bluuebunny/crossref_metadata_2025 huggingface dataset:
Proliferation Cycle Transcriptomic Signatures are Strongly associated With Gastric Cancer Patient Survival
Authors: Hu Jianwen , Yang Yanpeng , Ma Yongchen , Ning Yingze , Chen Guowei , Liu Yucun
Published: December 2021

Gastric cancer is one of the most heterogeneous tumors with multi-level molecular disturbances. Sustaining proliferative signaling and evading growth suppressors are two important hallmarks that enable the cancer cells to become tumorigenic and ultimately malignant, which enable tumor growth. Discovering and understanding the difference in tumor proliferation cycle phenotypes can be used to better classify tumors, and provide classification schemes for disease diagnosis and treatment options, which are more in line with the requirements of today’s precision medicine. We collected 691 eligible samples from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database, combined with transcriptome data, to explore different heterogeneous proliferation cycle phenotypes, and further study the potential genomic changes that may lead to these different phenotypes in this study. Interestingly, two subtypes with different clinical and biological characteristics were identified through cluster analysis of gastric cancer transcriptome data. The repeatability of the classification was confirmed in an independent Gene Expression Omnibus validation cohort, and consistent phenotypes were observed. These two phenotypes showed different clinical outcomes, and tumor mutation burden. This classification helped us to better classify gastric cancer patients and provide targeted treatment based on specific transcriptome data.
Exploring the Mechanism of Action of Canmei Formula Against Colorectal Adenoma Through Multi-Omics Technique
Authors: Guo Cui , Liu Xiaoqiang , Xu Yimin , Han Xinyue , Xie Runnan , Meng Xiangxue , Li Yuan , Chen Tongyu , Cheng Zhihong , Fu Xiaoling
Published: December 2021

Background: Canmei formula (CMF) is a traditional Chinese medicine compound with definite effect on the prevention and treatment of colorectal adenoma (CRA). CMF can prevent the transformation of intestinal inflammation to cancer. This study explored the mechanism of action of CMF in anti-CRA using multi-omics techniques.

Method: The mice were randomly divided into four groups: blank group (Control), high-fat diet (HFD) + AOM/DSS colorectal adenoma model (ADH) groups, Canmei formula treatment group (ADH-CMF) and sulfasalazine treatment group (Sul). Except for the blank group, ADH model was established in the other three groups by intraperitoneal injection with AOM reagent, and then mice were given 2.5% DSS in free drinking water and high-fat diet. The mice in the blank group and ADH groups were intragastrically perfused with normal saline, and the mice in the other two groups were treated with corresponding drugs for 20 weeks. During this period, the changes of physical signs of mice in each group were observed. The differentially expressed genes and proteins in the Control group, ADH group and ADH-CMF group were detected by RNA-seq transcriptome sequencing and Tandem Mass Tags (TMT) quantitative proteomics. After the combined analysis and verification, the key targets were analyzed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Moreover, the changes of intestinal flora in mice of the three groups were examined.

Results: A total of 2,548 differential genes were obtained by transcriptomics analysis, and 45 differential proteins were obtained by proteomics analysis. The results of proteomics data and experimental verification showed that CMF mainly affected the Phospholysine Phosphohistidine Inorganic Pyrophosphate Phosphatase (LHPP) target. GO analysis showed that the targets of CMF were involved in the biological processes such as cellular process, metabolic process and biological regulation. KEGG analysis showed that those genes were involved in oxidative phosphorylation, cell senescence, and metabolic pathways. Studies have shown that LHPP overexpression impeded colorectal cancer cell growth and proliferation in vitro, and was associated with a change in PI3K/AKT activity. The results of 16S DNA high-throughput sequencing showed that CMF could effectively regulate the abundance of Bifidobacterium, Candidatus_Saccharimonas and Erysipelatoclostridium in the intestinal flora at the genus level.

Conclusion: CMF regulates LHPP via the PI3K/AKT signaling pathway. CMF affects the abundance of specific intestinal flora and can regulate the disorder of intestinal flora to achieve the role of prevention and treatment of CRA.
Cellulose-Based Materials for Water Remediation: Adsorption, Catalysis, and Antifouling
Authors: Abdelhamid Hani Nasser , Mathew Aji P.
Published: December 2021

Cellulose-based materials have been advanced technologies that used in water remediation. They exhibit several advantages being the most abundant biopolymer in nature, high biocompatibility, and contain several functional groups. Cellulose can be prepared in several derivatives including nanomaterials such as cellulose nanocrystals (CNCs), cellulose nanofibrils (CNFs), and TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl radical)-mediated oxidized cellulose nanofibrils (TOCNF). The presence of functional groups such as carboxylic and hydroxyls groups can be modified or grafted with organic moieties offering extra functional groups customizing for specific applications. These functional groups ensure the capability of cellulose biopolymers to be modified with nanoparticles such as metal-organic frameworks (MOFs), graphene oxide (GO), silver (Ag) nanoparticles, and zinc oxide (ZnO) nanoparticles. Thus, they can be applied for water remediation via removing water pollutants including heavy metal ions, organic dyes, drugs, and microbial species. Cellulose-based materials can be also used for removing microorganisms being active as membranes or antibacterial agents. They can proceed into various forms such as membranes, sheets, papers, foams, aerogels, and filters. This review summarized the applications of cellulose-based materials for water remediation via methods such as adsorption, catalysis, and antifouling. The high performance of cellulose-based materials as well as their simple processing methods ensure the high potential for water remediation.
Vaccine Hesitancy and Support for Employer Vaccine Mandates
Authors: Ashwell Douglas , Cullinane Joanna , Croucher Stephen M
Published: December 2021

This study investigated COVID-19 vaccine hesitancy and support for employer vaccine mandates and support for termination for non-vaccinated employees among a national sample in New Zealand. A total of 1852 individuals participated in the study. Results indicated participants who are able to get vaccinated are less likely to support employer mandated vaccinations and the rights of employers to terminate employees who refuse to get vaccinated. However, individuals who self-identify that they can get vaccinated and have higher confidence in the COVID-19 vaccine are more likely to get vaccinated. Age and confidence in the vaccine influence support for mandates, while age and political affiliation influenced support for employer right to terminate a non-vaccinated employee. Understanding support, or lack thereof, for such initiatives is essential as businesses and nations respond to growing COVID concerns.
Emotionalism Within People-Oriented Software Design
Authors: Sherkat Mohammadhossein , Miller Tim , Mendoza Antonette , Burrows Rachel
Published: December 2021

In designing most software applications, much effort is placed upon the functional goals, making a software system useful. However, the failure to consider emotional goals, which make a software system pleasurable to use, can result in disappointment and system rejection even if utilitarian goals are well implemented. Although several studies have emphasised the importance of people’s emotional goals in developing software, there is little advice on how to address these goals in the software system development process. This paper bridges the gap between emotional goals elicitation and the software system design process by proposing a novel technique entitled the Emotional Goal Systematic Analysis Technique (EG-SAT) to systematically analyse people’s emotional goals in cooperation with functional and quality goals. EG-SAT allows in-depth analysis of emotional goals to build a software system and provides a visual notation for representing the analysis, facilitating communication and documentation. EG-SAT provides traceability of emotional goals in system design by connecting the emotional goals to functional and quality goals. To demonstrate the method in use, a two-part evaluation is conducted. First, EG-SAT is used to analyse the emotional goals of potential users of a mobile learning application that provides information about low carbon living for tradespeople and professionals in the building industry in Australia. The results of using EG-SAT in this case study are compared with a professionally developed baseline. Second, we ran a semi-controlled experiment in which 12 participants were asked to apply EG-SAT and another technique to our case study. The outcomes show that EG-SAT helped participants analyse emotional goals and gain valuable insights about the functional and non-functional goals for addressing people’s emotional goals. The key novelty of the EG-SAT is in proposing an easy to learn and easy to use technique that helps system analysts gain insights on how to address people’s emotional goals. Furthermore, the EG-SAT enables system analysts to convert emotional goals to traditional functional and non-functional goals that existing software engineering methodologies can analyse without demanding excessive effort.
The Prognostic Value of Lung Ultrasound in Patients With Newly Diagnosed Heart Failure With Preserved Ejection Fraction in the Ambulatory Setting
Authors: Morvai-Illés Blanka , Polestyuk-Németh Nóra , Szabó István Adorján , Monoki Magdolna , Gargani Luna , Picano Eugenio , Varga Albert , Ágoston Gergely
Published: December 2021

Background: Heart failure with preserved ejection fraction (HFpEF) is a growing healthcare burden, and its prevalence is steadily increasing. Lung ultrasound (LUS) is a promising screening and prognostic tool in the heart failure population. However, more information on its value in predicting outcome is needed.

Aims: The aim of our study was to assess the prognostic performance of LUS B-lines compared to traditional and novel clinical and echocardiographic parameters and natriuretic peptide levels in patients with newly diagnosed HFpEF in an ambulatory setting.

Methods: In our prospective cohort study, all ambulatory patients with clinical suspicion of HFpEF underwent comprehensive echocardiography, lung ultrasound and NT-proBNP measurement during their first appointment at our cardiology outpatient clinic. Our endpoint was a composite of worsening heart failure symptoms requiring hospitalization or loop diuretic dose escalation and death.

Results: We prospectively enrolled 75 consecutive patients with HFpEF who matched our inclusion and exclusion criteria. We detected 11 events on a 26 ± 10-months follow-up. We found that the predictive value of B-lines is similar to the predictive value of NT-proBNP (AUC 0.863 vs. 0.859), with the best cut-off at >15 B-lines. Having more B-lines than 15 significantly increased the likelihood of adverse events with a hazard ratio of 20.956 (p = 0.004). The number of B-lines remained an independent predictor of events at multivariate modeling. Having more than 15 B-lines lines was associated with a significantly worse event-free survival (Log-rank: 16.804, p < 0.001).

Conclusion: The number of B-lines seems to be an independent prognostic factor for adverse outcomes in HFpEF. Since it is an easy-to-learn, feasible and radiation-free method, it may add substantial value to the commonly used diagnostic and risk stratification models.
Kinematic Boundary Conditions Favouring Subduction Initiation at Passive Margins Over Subduction at Mid-oceanic Ridges
Authors: Auzemery A. , Willingshofer E. , Yamato P. , Duretz T. , Beekman F.
Published: December 2021

We perform numerical modelling to simulate the shortening of an oceanic basin and the adjacent continental margins in order to discuss the relationship between compressional stresses acting on the lithosphere and the time dependent strength of the mid-oceanic ridges within the frame of subduction initiation. We focus on the role of stress regulating mechanisms by testing the stress–strain-rate response to convergence rate, and the thermo-tectonic age of oceanic and continental lithospheres. We find that, upon compression, subduction initiation at passive margin is favoured for thermally thin (Palaeozoic or younger) continental lithospheres (<160 km) over cratons (>180 km), and for oceanic basins younger than 60 Myr (after rifting). The results also highlight the importance of convergence rate that controls stress distribution and magnitudes in the oceanic lithosphere. Slow convergence (<0.9 cm/yr) favours strengthening of the ridge and build-up of stress at the ocean-continent transition allowing for subduction initiation at passive margins over subduction at mid-oceanic ridges. The results allow for identifying geodynamic processes that fit conditions for subduction nucleation at passive margins, which is relevant for the unique case of the Alps. We speculate that the slow Africa–Europe convergence between 130 and 85 Ma contributes to the strengthening of the mid-oceanic ridge, leading to subduction initiation at passive margin 60–70 Myr after rifting and passive margin formation.
Noble Metals in Arc Basaltic Magmas Worldwide: A Case Study of Modern and Pre-Historic Lavas of the Tolbachik Volcano, Kamchatka
Authors: Kutyrev Anton , Zelenski Michael , Nekrylov Nikolai , Savelyev Dmitry , Kontonikas-Charos Alkiviadis , Kamenetsky Vadim S.
Published: December 2021

Platinum-group elements (PGE) and gold are a promising tool to assess the processes of mantle melting beneath the subduction zones. However, fractionation processes in magmas inevitably overwrite the initial metal budgets of magmas, making constraints on the melting processes inconclusive. Moreover, little is still known about the geochemical behavior of a particular metal in a single arc magmatic system, from mantle melting towards magma solidification. Here we compare noble metals in lavas from several eruptions of the Tolbachik volcano (Kamchatka arc) to better understand the effects of magma differentiation, estimate primary melt compositions and make constraints on the mantle melting. We show that Ir, Ru, Rh and, to a lesser extent, Pt are compatible during magmatic differentiation. The pronounced incompatible behavior of Cu and Pd, observed in Tolbachik magmas, rules out the significant influence of sulfide melts on the early magmatic evolution in this particular case. Gold is also incompatible during magmatic differentiation; however, its systematics can be affected by the inferred gold recycling in the plumbing system of Tolbachik. Although the Tolbachik lavas show only slightly higher PGE fractionation than in MORB, a notable negative Ru anomaly (higher Pt/Ru and Ir/Ru) is observed. We attribute this to be a result of greater oxidation in the subarc mantle (by 1–4 log units), which promotes crystallization of Ru-bearing phases such as Fe3+-rich Cr-spinel and laurite. The estimated Pd contents for the parental melt of the Tolbachik lavas approaches 6.5 ppb. This is several times higher than reported MORB values (1.5 ± 0.5 ppb), suggesting the enrichment of Pd in the mantle wedge. Our results highlight the influence of the subduction-related processes and mantle wedge refertilization on the noble metal budgets of arc magmas.
Multi-Step Combined Control Technology for Karst and Fissure Water Inrush Disaster During Shield Tunneling in Spring Areas
Authors: Huang Xing , Li Linfeng , Zhang Chaofan , Liu Bin , Li Kejin , Shi Hongbing , Jing Boyu
Published: December 2021

Shield tunneling in highly fractured karst water-rich conditions easily results in water inrush disaster or even causes the roof of the karst caves to collapse. Severe water inrush disasters have occurred during the EPB (earth pressure balance) shield machine of the Jinan Metro Line R1 advanced through a karst and fissure groundwater-rich limestone ground in the spring area. To cope with the extreme water inrush risk, a multi-step combined control technology was put forward. First, a detailed geological exploration was carried out by ahead geophysical prospecting using high-density resistivity method, geological radar, etc., and geological borehole drilling was conducted from the ground surface before excavation. As a result, the distribution orientation, size, fissure development degree, and water inflow channel within the surrounding rock of the karst caves were detected. Second, multi-step grouting was performed to reinforce the surrounding rock, including pre-grouting treatment and filling rock blocks to the big karst caves from the ground surface, multiple grouting with a small amount of inert slurry each time inside the tunnel, and secondary circumferential hoop grouting at the shield tail. Third, the tunneling process was optimized, including optimizing the tunneling parameters, making full use of the air-pressurized tunneling technology of the EPB to press bentonite into the fractures around the excavation cabin to seal the fissure water, and using the drainage system of EPB and muck improvement technology to reduce the water inrush disaster. Meanwhile, shield protection slurry technology is applied to cutter inspection and replacement in the pressurized chamber under dynamic water flow environment of the spring terrain. The practice shows that the water inrush on the tunnel face is obviously alleviated after the shield machine advanced into the grouting area. According to statistics, the water inflow on the tunnel face decreases from about 4 m3/h before treatment to less than 0.3 m3/h after the abovementioned control, and the water seepage between the segmental linings reduces to almost zero. The average advance rate increased from 3 m/day without stopping or even zero when the shield machine needs to shut down 2–3 days for drainage to about 6 m/day. In addition, the treatments prevented the shield machine from jamming and the head descending disaster. This study provided a reliable control method for shield tunneling through the karst and fissure water-rich area and played an essential role in protecting the spring water.
Efficient Seismic Stability Analysis of Embankment Slopes Subjected to Water Level Changes Using Gradient Boosting Algorithms
Authors: Wang Luqi , Wu Jiahao , Zhang Wengang , Wang Lin , Cui Wei
Published: December 2021

Embankments are widespread throughout the world and their safety under seismic conditions is a primary concern in the geotechnical engineering community since the failure events may lead to disastrous consequences. This study proposes an efficient seismic slope stability analysis approach by introducing advanced gradient boosting algorithms, namely Categorical Boosting (CatBoost), Light Gradient Boosting Machine (LightGBM), and Extreme Gradient Boosting (XGBoost). A database consisting of 600 datasets is prepared for model calibration and evaluation, where the factor of safety (FS) is regarded as the output and four influential factors are selected as the inputs. For each dataset, the FS corresponding to the four inputs is evaluated using the commercial geotechnical software of Slide2. As an illustration, the proposed approach is applied to the seismic stability analysis of a hypothetical embankment example subjected to water level changes. For comparison, the predictive performance of CatBoost, LightGBM, and XGBoost is investigated. Moreover, the Shapley additive explanations (SHAP) method is used in this study to explore the relative importance of the four features. Results show that all the three gradient boosting algorithms (i.e., CatBoost, LightGBM, and XGBoost) perform well in the prediction of FS for both the training dataset and testing dataset. Among the four influencing factors, the friction angle φ is the most important feature variable, followed by horizontal seismic coefficient Kh, cohesion c, and saturated permeability ks.
Coupling of Anaerobic Digestion and Struvite Precipitation in the Same Reactor: Effect of Zeolite and Bischofite as Mg2+ Source
Authors: Palominos N. , Castillo A. , Guerrero L. , Borja R. , Huiliñir C.
Published: December 2021

The aim of this research was to assess the simultaneous effect of zeolite and bischofite on estruvite production in an anaerobic digester treating pig slurry as substrate. Three ratios (5:1, 6:1 and 7:1) of Mg-P were used for evaluating the effect of only bischofite on anaerobic digestion. For assessing the simultaneous effect of zeolite and bischofite on anaerobic digestion, three mass ratios of zeolite:bischofite (1, 5 and 10%) were used. As results, bischofite as Mg+2 source served to decrease the total phosphorous (TP) concentration in the anaerobic digestion of pig manure without affecting the maximum methane production rate or methane yield of the system. An average 82.5% TP removal was found in the reactors with bischofite during the first 5 days of digestion. Nevertheless, bischofite increased the lag-phase of the system. The simultaneous presence of zeolite and bischofite (1% ratio with respect to bischofite) caused a TP removal of 65.6% and increased the methane yield by up to 19.9% compared to a system without zeolite or bischofite. Thus, it is feasible to use bischofite and zeolite as enhancers for the simultaneous production of biogas and struvite inside an anaerobic digester treating piggery wastewater.
Variation of Small and Large Wild Bee Communities Under Honeybee Pressure in Highly Diverse Natural Habitats
Authors: Demeter Imre , Balog Adalbert , Sárospataki Miklós
Published: December 2021

During the study, the honeybee effects on wild bees were tested and hypothesized that smaller distances from beehives will increase competitions between honeybees and wild bees, while greater distances will have a deleterious effect on competition. The impact on species richness and diversity was tested with distances from beehives, considering that this may differ when large and small wild bee species are considered separately. Altogether 158 species and 13,164 individuals were collected, from which 72% (9,542 individuals) were Apis mellifera. High variation in abundances was detected from one year to another, and the species turnover by sites was 67% in site A, 66% in site V, and 63% in site F. This last one was the site with the previous contact with honeybees. Considering distances from beehives, significant decreases in small bee species diversity were detected from one year to another at each distance except site F, 250 m from hives. The changes in species diversity and community structure of small bee species are detected from one year to another.
Influence of High Temperatures and Heat Wave on Thermal Biology, Locomotor Performance, and Antioxidant System of High-Altitude Frog Nanorana pleskei Endemic to Qinghai-Tibet Plateau
Authors: He Jie , Tang Xiaolong , Pu Peng , Zhang Tao , Niu Zhiyi , Meng Fei , Xi Lu , Ma Ming , Wu Juan , Ma Miaojun , Chen Qiang
Published: December 2021

Investigating how highland amphibians respond to changes in ambient temperature may be of great significance for their fate prediction and effective conservation in the background of global warming. Here, using field individuals as the control group, we investigated the influence of high temperatures (20.5 and 25.5°C) and heat wave (15–26.6°C) on the thermal preference, critical thermal limits, locomotor performance, oxidative stress, and antioxidant enzyme activities in high-altitude frog Nanorana pleskei (3,490 m) endemic to the Qinghai-Tibet Plateau (QTP). After 2 weeks of acclimation to high temperatures and heat wave, the thermal preference (Tpref), critical thermal maximum (CTmax), and range of tolerable temperature significantly increased, while the critical thermal minimum (CTmin) was significantly decreased. The total time of jump to exhaustion significantly decreased, and burst swimming speed significantly increased in frogs acclimated in the high temperature and heat wave groups compared with the field group. In the high temperature group, the level of H2O2 and lipid peroxide (malondialdehyde, MDA), as well as the activities of glutathione peroxidase (GPX), glutathione reductase (GR), catalase (CAT), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC) significantly increased in the liver or muscle. However, in the heat wave group, the MDA content significantly decreased in the liver, and antioxidants activities decreased in the liver and muscle except for CAT activities that were significantly increased in the liver. These results indicated that N. pleskei could respond to the oxidative stress caused by high temperatures by enhancing the activity of antioxidant enzymes. The heat wave did not appear to cause oxidative damage in N. pleskei, which may be attributed to the fact that they have successfully adapted to the dramatic temperature fluctuations on the QTP.
Transgene-free Genome Editing in Plants
Authors: Gu Xiaoyong , Liu Lijing , Zhang Huawei
Published: December 2021

Genome editing is widely used across plant species to generate and study the impact of functional mutations in crop improvement. However, transgene integration in plant genomes raises important legislative concerns regarding genetically modified organisms. Several strategies have been developed to remove or prevent the integration of gene editor constructs, which can be divided into three major categories: 1) elimination of transgenic sequences via genetic segregation; 2) transient editor expression from DNA vectors; and 3) DNA-independent editor delivery, including RNA or preassembled Cas9 protein-gRNA ribonucleoproteins (RNPs). Here, we summarize the main strategies employed to date and discuss the advantages and disadvantages of using these different tools. We hope that our work can provide important information concerning the value of alternative genome editing strategies to advance crop breeding.
Genetic Landscape of Relapsed and Refractory Diffuse Large B-Cell Lymphoma: A Systemic Review and Association Analysis With Next-Generation Sequencing
Authors: Gao Fan , Tian Lei , Shi Hui , Zheng Peihao , Wang Jing , Dong Fei , Hu Kai , Ke Xiaoyan
Published: December 2021

In our research, we screened 1,495 documents, compiled the whole-exome sequencing data of several studies, formed a data set including 92 observations of RRDLBCL (Relapsed and refractory diffuse large B-cell lymphoma), and performed association analysis on the high-frequency mutations among them. The most common mutations in the data set include TTN, KMT2D, TP53, IGLL5, CREBBP, BCL2, MYD88, and SOCS1 etc. Among these, CREBBP, KMT2D, and BCL2 have a strong association with each other, and SOCS1 has a strong association with genes such as STAT6, ACTB, CIITA, ITPKB, and GNA13. TP53 lacks significant associations with most genes. Through SOM clustering, expression-level analysis and protein interaction analysis of common gene mutations, we believe that RRDLBCL can be divided into five main types. We tested the function of the model and described the clinical characteristics of each subtype through a targeted sequencing RRDLBCL cohort of 96 patients. The classification is stated as follows: 1) JAK-STAT-related type: including STAT6, SOCS1, CIITA, etc. The genetic lineage is similar to PMBL and cHL. Retrospective analysis suggests that this subtype responds poorly to induction therapy (R-CHOP, p < 0.05). 2) BCL-CREBBP type: Epigenetic mutations such as KMT2D and CREBBP are more common in this type, and are often accompanied by BCL2 and EZH2 mutations. 3) MCD type: including MYD88 and CD79B, PIM1 is more common in this subtype. 4) TP53 mutation: TP53 mutant patients, which suggests the worst prognosis (p < 0.05) and worst response to CART treatment. 5) Undefined type (Sparse item type): Major Genetic Change Lacking Type, which has a better prognosis and better response to CART treatment. We also reviewed the literature from recent years concerning the previously mentioned common gene mutations.
Pseudo-188D: Phage Protein Prediction Based on a Model of Pseudo-188D
Authors: Gu Xiaomei , Guo Lina , Liao Bo , Jiang Qinghua
Published: December 2021

Phages have seriously affected the biochemical systems of the world, and not only are phages related to our health, but medical treatments for many cancers and skin infections are related to phages; therefore, this paper sought to identify phage proteins. In this paper, a Pseudo-188D model was established. The digital features of the phage were extracted by PseudoKNC, an appropriate vector was selected by the AdaBoost tool, and features were extracted by 188D. Then, the extracted digital features were combined together, and finally, the viral proteins of the phage were predicted by a stochastic gradient descent algorithm. Our model effect reached 93.4853%. To verify the stability of our model, we randomly selected 80% of the downloaded data to train the model and used the remaining 20% of the data to verify the robustness of our model.
The CTRP3-AdipoR2 Axis Regulates the Development of Experimental Autoimmune Encephalomyelitis by Suppressing Th17 Cell Differentiation
Authors: Murayama Masanori A. , Chi Hsi-Hua , Matsuoka Mako , Ono Takahiro , Iwakura Yoichiro
Published: December 2021

C1q/TNF-related proteins (CTRP) including CTRP3 are a group of secreted proteins which have a complement C1q-like domain in common, and play versatile roles in lipid metabolism, inflammation, tumor metastasis and bone metabolism. Previously, we showed that the expression of C1qtnf3, encoding CTRP3, is highly augmented in joints of autoimmune arthritis models and CTRP3-deficiency exacerbates collagen-induced arthritis in mice. However, the mechanisms how CTRP3-deficiency exacerbates arthritis still remain to be elucidated. In this study, we showed that CTRP3 was highly expressed in Th17 cell, a key player for the development of autoimmune diseases, and Th17 cell differentiation was augmented in C1qtnf3–/– mice. Th17 cell differentiation, but not Th1 cell differentiation, was suppressed by CTRP3 and this suppression was abolished by the treatment with a receptor antagonist against AdipoR2, but not AdipoR1, associated with suppression of Rorc and Stat3 expression. Furthermore, AdipoR1 and AdipoR2 agonist, AdipoRon suppressed Th17 cell differentiation via AdipoR2, but not AdipoR1. The development of myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis was enhanced in C1qtnf3–/– mice associated with increase of Th17 cell population. CTRP3 inhibited MOG-induced IL-17 production from T cells by affecting both T cells and dendritic cells. These results show that CTRP3 is an endogenous regulator of Th17 differentiation, suggesting that the CTRP3-AdipoR2 axis is a good target for the treatment of Th17 cell-mediated diseases.
Vitamin D Metabolic Pathway Genes Polymorphisms and Their Methylation Levels in Association With Rheumatoid Arthritis
Authors: Zhang Tian-Ping , Li Hong-Miao , Huang Qian , Wang Li , Li Xiao-Mei
Published: December 2021

Abnormal vitamin D metabolism is involved in the pathogenesis of rheumatoid arthritis (RA). In this study, we evaluated the association of single nucleotide polymorphisms (SNPs) and methylation levels in vitamin D metabolic pathway genes with RA susceptibility. Ten SNPs in vitamin D metabolic pathway genes (CYP2R1, CYP24A1, VDR, CYP27B1) were genotyped in 477 RA patients and 496 controls by improved multiple ligase detection reaction (iMLDR). The methylation levels of the promoter regions of these genes were detected in 122 RA patients and 123 controls using Illumina Hiseq platform. We found that the CYP2R1 rs1993116 GA genotype, CYP27B1 rs4646536 GA genotype, rs4646536 A allele frequencies were significantly increased in RA patients when compared to controls. The decreased risk of rs1993116, rs4646536 was found under the dominant mode in RA patients. However, no significant association was found between CYP2R1 rs7936142, rs12794714, CYP24A1 rs2762934, rs6068816, rs2296239, rs2296241, VDR rs11574129, rs3847987 polymorphism, and RA susceptibility. The VDR, CYP27B1 methylation levels in RA patients were significantly lower than those in controls, while CYP2R1, CYP24A1 methylation levels were not associated with RA. There were no statistical associations between CYP2R1, CYP24A1, VDR, CYP27B1 methylation levels and their respective genotype in RA patients. In addition, plasma 25OHD level in RA patients was significantly lower than that in healthy controls. In summary, our results showed that CYP2R1, CYP27B1 genetic variations were associated with the genetic background of RA, while altered VDR, CYP27B1 methylation levels were related to the risk of RA.
The Underrated Salivary Virome of Men Who Have Sex With Men Infected With HIV
Authors: Guo Ying , Huang Xiaojie , Sun Xintong , Yu Yixi , Wang Yan , Zhang Baojin , Cao Jie , Wen Shuo , Li Yuchen , Wang Xin , Cai Siyu , Xia Wei , Wei Feili , Duan Junyi , Dong Haozhi , Guo Shan , Zhang Fengqiu , Zheng Dongxiang , Sun Zheng
Published: December 2021

Salivary virome is important for oral ecosystem, but there are few reports on people living with HIV. We performed metagenomic sequencing to compare composition and functional genes of salivary virobiota between one HIV-negative and four HIV-positive groups in which participants were all men who have sex with men (MSM) with different immunosuppression statuses (five samples per group) to find the evidence that salivary virobiota plays a role in the pathogenesis of oral disease. Acute-stage subjects achieved a positive result of HIV RNA, but HIV antibody negative or indeterminate, whereas individuals with mild, moderate, and severe immunosuppression exhibited CD4+ T-lymphocyte counts of at least 500, 200–499, and less than 200 cells/μL or opportunistic infection, respectively. The results showed the composition of salivary virus genera in subjects with mild immunosuppression was the most similar to that in healthy people, followed by that in the acute stage; under severe immunosuppression, virus genera were suppressed and more similar to that under moderate immunosuppression. Furthermore, abnormally high abundance of Lymphocryptovirus was particularly obvious in MSM with HIV infection. Analysis of KEGG Pathway revealed that Caulobacter cell cycle, which affects cell duplication, became shorter in HIV-positive subjects. It is worth noting that in acute-stage participants, protein digestion and absorption related to the anti-HIV-1 activity of secretory leukocyte protease inhibitor was increased. Moreover, in the severely immunosuppressed subjects, glutathione metabolism, which is associated with the activation of lymphocytes, was enhanced. Nevertheless, the ecological dysbiosis in HIV-positive salivary virobiota possibly depended on the changes in blood viral load, and salivary dysfunction of MSM infected with HIV may be related to CD4 counts. Ribonucleoside diphosphate reductase subunit M1 in purine metabolism was negatively correlated, though weakly, to CD4 counts, which may be related to the promotion of HIV-1 DNA synthesis in peripheral blood lymphocytes. 7-Cyano-7-deazaguanine synthase in folate biosynthesis was weakly positively correlated with HIV viral load, suggesting that this compound was produced excessively to correct oral dysfunction for maintaining normal cell development. Despite the limited number of samples, the present study provided insight into the potential role of salivary virome in the oral function of HIV infected MSM.
Th1/Th17 T cell Tissue-Resident Immunity Increases Protection, But Is Not Required in a Vaccine Strategy Against Genital Infection With Chlamydia trachomatis
Authors: Nguyen Nina Dieu Nhien Tran , Guleed Safia , Olsen Anja Weinreich , Follmann Frank , Christensen Jan Pravsgaard , Dietrich Jes
Published: December 2021

The requirement for vaccine-induced tissue-resident immunity for protection against one or repeated infections with Chlamydia trachomatis (C.t.) is still not fully resolved. In this study, our aim was to investigate to which degree tissue-resident Th1/Th17 T cells in the genital tract (GT) could add to the protection mediated by circulating immunity. Out of several mucosal vaccine strategies, a strategy termed SIM (for simultaneous intrauterine and parenteral immunization with CAF01 adjuvanted CTH522), was superior in generating genital tract tissue-resident Th1/Th17 T cell immunity. This led to a faster and stronger local CD4 T cell response post infection, consisting of multifunctional IFNγ/TNFα-producing Th1 T cells and IFNγ/TNFα/IL-17-producing Th17 T cells, and a faster recruitment of innate immune cells. Post infection, SIM animals showed an additional significant reduction in bacterial levels compared to mice having received only a parenteral vaccine. Nevertheless, the parenteral strategy reduced bacterial levels by 75%, and interestingly, post infection, these mice generated their own vaccine-derived genital tract tissue-resident memory Th1/Th17 T cells, which upon a subsequent infection showed as fast an activation in the genital tract, as observed in SIM mice. Furthermore, in contrast to after the first infection, both groups of mice now showed a similar infection-induced boost in local vaginal IgA and IgG titers. Thus, vaccine-induced resident immunity, generated pre-infection, led to an advantage in the response against the first infection, but not the second infection, suggesting that a parenteral vaccine strategy is a suitable vaccine strategy against infections with Chlamydia trachomatis.
Fine-Scale Mapping of Mega-Epibenthic Communities and Their Patch Characteristics on Two New Zealand Seamounts
Authors: Goode Savannah L. , Rowden Ashley A. , Bowden David A. , Clark Malcolm R. , Stephenson Fabrice
Published: December 2021

Seamounts are common features of the deep seafloor that are often associated with aggregations of mega-epibenthic fauna, including deep-sea corals and sponges. Globally, many seamounts also host abundant fish stocks, supporting commercial bottom trawl fisheries that impact non-target benthic species through damage and/or removal of these non-target species. However, the effects of bottom trawling on seamount benthic communities, as well as their recovery potential, will vary over the total seamount area because of differences in within seamount habitat and community structure. It is therefore important to understand fine-scale community dynamics, community patch characteristics, and the environmental drivers contributing to these patterns to improve habitat mapping efforts on seamounts and to determine the potential for benthic communities on seamounts to recover from fishing disturbances. Here we analysed the structure and distribution of mega-epibenthic communities on two New Zealand seamounts with different physical environments to determine which environmental variables best correlated with variation in community structure within each seamount. We used the identified environmental variables to predict the distribution of communities beyond the sampled areas, then described the spatial patterns and patch characteristics of the predicted community distributions. We found the environmental variables that best explained variations in community structure differed between the seamounts and at different spatial scales. These differences were reflected in the distribution models: communities on one seamount were predicted to form bands with depth, while on the other seamount communities varied mostly with broadscale aspect and the presence of small pinnacles. The number and size of community patches, inter-patch distances, and patch connectedness were found to differ both within and between seamounts. These types of analyses and results can be used to inform the spatial management of seamount ecosystems.
Effects of Measuring Devices and Sampling Strategies on the Interpretation of Monitoring Data for Long-Term Trend Analysis
Authors: Fischer Philipp , Dietrich Peter , Achterberg Eric P. , Anselm Norbert , Brix Holger , Bussmann Ingeborg , Eickelmann Laura , Flöser Götz , Friedrich Madlen , Rust Hendrik , Schütze Claudia , Koedel Uta
Published: December 2021

A thorough and reliable assessment of changes in sea surface water temperatures (SSWTs) is essential for understanding the effects of global warming on long-term trends in marine ecosystems and their communities. The first long-term temperature measurements were established almost a century ago, especially in coastal areas, and some of them are still in operation. However, while in earlier times these measurements were done by hand every day, current environmental long-term observation stations (ELTOS) are often fully automated and integrated in cabled underwater observatories (UWOs). With this new technology, year-round measurements became feasible even in remote or difficult to access areas, such as coastal areas of the Arctic Ocean in winter, where measurements were almost impossible just a decade ago. In this context, there is a question over what extent the sampling frequency and accuracy influence results in long-term monitoring approaches. In this paper, we address this with a combination of lab experiments on sensor accuracy and precision and a simulated sampling program with different sampling frequencies based on a continuous water temperature dataset from Svalbard, Arctic, from 2012 to 2017. Our laboratory experiments showed that temperature measurements with 12 different temperature sensor types at different price ranges all provided measurements accurate enough to resolve temperature changes over years on a level discussed in the literature when addressing climate change effects in coastal waters. However, the experiments also revealed that some sensors are more suitable for measuring absolute temperature changes over time, while others are more suitable for determining relative temperature changes. Our simulated sampling program in Svalbard coastal waters over 5 years revealed that the selection of a proper sampling frequency is most relevant for discriminating significant long-term temperature changes from random daily, seasonal, or interannual fluctuations. While hourly and daily sampling could deliver reliable, stable, and comparable results concerning temperature increases over time, weekly sampling was less able to reliably detect overall significant trends. With even lower sampling frequencies (monthly sampling), no significant temperature trend over time could be detected. Although the results were obtained for a specific site, they are transferable to other aquatic research questions and non-polar regions.
Environmental Variability and Threshold Model’s Predictions for Coral Reefs
Authors: McClanahan Tim Rice , Azali Maxwell Kodia
Published: December 2021

Current models of the future of coral reefs rely on threshold (TM) and multivariate environmental variability models (VM) that vary in how they account for spatial and temporal environmental heterogeneity. Here, a VM based on General Additive Model (GAM) methods evaluated the empirical relationships between coral cover (n= 905 sites pooled to 318 reef cells of the Western and Central Indian Ocean Provinces) and 15 potentially influential variables. Six environmental and one fisheries management variables were selected as significant including SST shape distributions, dissolved oxygen, calcite, and fisheries management. Common predictive variables, including cumulative degree-heating weeks (DHW), pH, maximum light, SST bimodality and rate of rise, and two multivariate metrics were either weak or not significant predictors of coral cover. A spatially-resolved 2020 baseline for future predictions of coral cover within 11,678 reef ∼6.25 km2cells within 13 ecoregions and 4 fisheries management categories using the 7 top VM variables was established for comparing VM and TM coral cover prediction for the year 2050. We compared the two model’s predictions for high and low Relative Concentration Pathway (CMIP5; RCP8.5 and 2.6) scenarios using the four available future-cast SST variables. The excess heat (DHW)-coral mortality relationship of the TM predicted considerably lower coral cover in 2050 than the VM. For example, for the RCP8.5 and RCP2.6 scenarios, the decline in coral for the TM predicted was 81 and 58% compared to a 29 and 20% for the VM among reef cells with >25% coral cover in 2020, if a proposed optimal fisheries management was achieved. Despite differences, coral cover predictions for the VM and TM overlapped in two environmental regions located in the southern equatorial current region of the Indian Ocean. Historical and future patterns of acute and chronic stresses are expected to be more influential than cumulative heat stress in predicting coral cover, which is better accounted for by the VM than the TM.
Using Case Studies to Investigate Cetacean Bycatch/Interaction Under-Reporting in Countries With Reporting Legislation
Authors: Basran Charla Jean , Sigurðsson Guðjón Már
Published: December 2021

Accurate reporting of cetacean bycatch in/interaction with fishing gear in fisher logbooks would be of immense scientific value; however, despite some countries having mandatory reporting laws, logbook reporting is widely considered unreliable and cetacean catches are thought to be under-reported. Despite this widespread notion of logbook unreliability, under-reporting has rarely been quantified. For this study, initially we compiled the first comprehensive legislation summary for countries which have cetacean bycatch/interaction reporting laws. We then used data provided by government and research agencies in three case study countries (New Zealand, United States, and Iceland) to test for differences between logbook and observer reported cetacean bycatch. Comparisons were made using paired t-tests and Wilcoxon tests with a set alpha of 0.05. Overall, cetacean bycatch recorded by observers was higher than that from fisher logbooks by an average of 774% in trawls, 7348% in nets, and 1725% in hook and line gears. When combining all years of data available, fisher logbook cetacean catch per unit efforts or average number of individuals caught were significantly less than those from observer data for all gear types that could be examined in all countries, except for lining in New Zealand. Overall, there was significant under-reporting in the case study countries despite differences in geographic location, cetacean species and density and EEZ size, suggesting these results would likely be similar in many countries with comparable, well-developed fishing industries. Under-reporting in logbooks, despite laws, was clearly quantified and it is known that fishers have little incentive to report and have concerns over negative repercussions to the industry over bycatch issues. If logbook reporting is to continue in some fisheries, clearer legislation, simplified reporting using new technology (such as smartphone apps) and combination with electronic monitoring cameras to verify compliance may improve reporting accuracy. The introduction of electronic monitoring, given its lower cost compared to observer programs and high accuracy, may be the most viable option to obtain reliable cetacean bycatch estimates, and could be considered to replace logbook reporting altogether.