bluuebunny/crossref_metadata_2025 huggingface dataset:
New Developments in Sparse PLS Regression
Authors: Magnanensi Jérémy , Maumy-Bertrand Myriam , Meyer Nicolas , Bertrand Frédéric
Published: July 2021

Methods based on partial least squares (PLS) regression, which has recently gained much attention in the analysis of high-dimensional genomic datasets, have been developed since the early 2000s for performing variable selection. Most of these techniques rely on tuning parameters that are often determined by cross-validation (CV) based methods, which raises essential stability issues. To overcome this, we have developed a new dynamic bootstrap-based method for significant predictor selection, suitable for both PLS regression and its incorporation into generalized linear models (GPLS). It relies on establishing bootstrap confidence intervals, which allows testing of the significance of predictors at preset type I risk α, and avoids CV. We have also developed adapted versions of sparse PLS (SPLS) and sparse GPLS regression (SGPLS), using a recently introduced non-parametric bootstrap-based technique to determine the numbers of components. We compare their variable selection reliability and stability concerning tuning parameters determination and their predictive ability, using simulated data for PLS and real microarray gene expression data for PLS-logistic classification. We observe that our new dynamic bootstrap-based method has the property of best separating random noise in y from the relevant information with respect to other methods, leading to better accuracy and predictive abilities, especially for non-negligible noise levels.
Direct Isomaltulose Synthesis From Beet Molasses by Immobilized Sucrose Isomerase
Authors: Wang Qin-Qing , Yang Ming , Hao Jian-Hua , Ma Zai-Chao
Published: July 2021

Isomaltulose is becoming a focus as a functional sweetener for sucrose substitutes; however, isomaltulose production using sucrose as the substrate is not economical. Low-cost feedstocks are needed for their production. In this study, beet molasses (BM) was introduced as the substrate to produce isomaltulose for the first time. Immobilized sucrose isomerase (SIase) was proved as the most efficient biocatalyst for isomaltulose synthesis from sulfuric acid (H2SO4) pretreated BM followed by centrifugation for the removal of insoluble matters and reducing viscosity. The effect of different factors on isomaltulose production is investigated. The isomaltulose still achieved a high concentration of 446.4 ± 5.5 g/L (purity of 85.8%) with a yield of 0.94 ± 0.02 g/g under the best conditions (800 g/L pretreated BM, 15 U immobilized SIase/g dosage, 40°C, pH of 5.5, and 10 h) in the eighth batch. Immobilized SIase used in repeated batch reaction showed good reusability to convert pretreated BM into isomaltulose since the sucrose conversion rate remained 97.5% in the same batch and even above 94% after 11 batches. Significant cost reduction of feedstock costs was also confirmed by economic analysis. The findings indicated that this two-step process to produce isomaltulose using low-cost BM and immobilized SIase is feasible. This process has the potential to be effective and promising for industrial production and application of isomaltulose as a functional sweetener for sucrose substitute.
Integrative Analysis of MUC4 to Prognosis and Immune Infiltration in Pan-Cancer: Friend or Foe?
Authors: Gao Xiao-Peng , Dong Jie-Jie , Xie Tian , Guan Xiaoqing
Published: July 2021

MUC4, a transmembrane mucin, plays important roles in epithelial renewal and differentiation. Recent studies suggest that MUC4 has been implicated in pancreatic cancer pathogenesis and is expressed in various normal and cancer tissues. The underlying features of MUC4 across various cancer types may allow us to ensure appropriate treatment and patient monitoring. However, the contributions of MUC4 to pan-cancer have not been well characterized. In this study, we investigated the expression pattern and prognostic value of MUC4 across multiple databases. We further explored genomic and epigenetic alterations of MUC4, its association with proliferation and metastasis, and the correlation with immune infiltration in different cancers. Our results characterized the distinct expression profile and prognostic values of MUC4 in pan-cancer. Through examining its association with genomic alteration, tumor proliferation, and metastasis, as well as tumor infiltration, we revealed multiple function effects of MUC4. MUC4 may influence prognosis, proliferation, metastasis, and immune response in opposite directions. In conclusion, our findings suggested the necessity to more carefully evaluate MUC4 as a biomarker and therapeutic target and develop the new antibodies for cancer detection and intervention.
To Better Generate Organoids, What Can We Learn From Teratomas?
Authors: Li Hongyu , Gao Lixiong , Du Jinlin , Ma Tianju , Ye Zi , Li Zhaohui
Published: July 2021

The genomic profile of animal models is not completely matched with the genomic profile of humans, and 2D cultures do not represent the cellular heterogeneity and tissue architecture found in tissues of their origin. Derived from 3D culture systems, organoids establish a crucial bridge between 2D cell cultures and in vivo animal models. Organoids have wide and promising applications in developmental research, disease modeling, drug screening, precision therapy, and regenerative medicine. However, current organoids represent only single or partial components of a tissue, which lack blood vessels, native microenvironment, communication with near tissues, and a continuous dorsal-ventral axis within 3D culture systems. Although efforts have been made to solve these problems, unfortunately, there is no ideal method. Teratoma, which has been frequently studied in pathological conditions, was recently discovered as a new in vivo model for developmental studies. In contrast to organoids, teratomas have vascularized 3D structures and regions of complex tissue-like organization. Studies have demonstrated that teratomas can be used to mimic multilineage human development, enrich specific somatic progenitor/stem cells, and even generate brain organoids. These results provide unique opportunities to promote our understanding of the vascularization and maturation of organoids. In this review, we first summarize the basic characteristics, applications, and limitations of both organoids and teratomas and further discuss the possibility that in vivo teratoma systems can be used to promote the vascularization and maturation of organoids within an in vitro 3D culture system.
Construction of T7-Like Expression System in Pseudomonas putida KT2440 to Enhance the Heterologous Expression Level
Authors: Liang Tianxin , Sun Jun , Ju Shuyun , Su Shenyi , Yang Lirong , Wu Jianping
Published: July 2021

Pseudomonas putida KT2440 has become an attractive chassis for heterologous expression with the development of effective genetic manipulation tools. Improving the level of transcriptional regulation is particularly important for extending the potential of P. putida KT2440 in heterologous expression. Although many strategies have been applied to enhance the heterologous expression level in P. putida KT2440, it was still at a relatively low level. Herein we constructed a T7-like expression system in P. putida KT2440, mimicking the pET expression system in Escherichia coli, which consisted of T7-like RNA polymerase (MmP1) integrated strain and the corresponding expression vector for the heterologous expression enhancement. With the optimization of the insertion site and the copy number of RNA polymerase (RNAP), the relative fluorescence intensity (RFI) of the super-folder green fluorescent protein (sfGFP) was improved by 1.4-fold in MmP1 RNAP integrated strain. The induction point and IPTG concentration were also optimized. This strategy was extended to the gene-reduced strain EM42 and the expression of sfGFP was improved by 2.1-fold. The optimal RNAP integration site was also used for introducing T7 RNAP in P. putida KT2440 and the expression level was enhanced, indicating the generality of the integration site for the T7 expression system. Compared to other inducible expression systems in KT2440, the heterologous expression level of the Mmp1 system and T7 system were more than 2.5 times higher. Furthermore, the 3.6-fold enhanced expression level of a difficult-to-express nicotinate dehydrogenase from Comamonas testosteroni JA1 verified the efficiency of the T7-like expression system in P. putida KT2440. Taken together, we constructed and optimized the T7-like and T7 expression system in P. putida, thus providing a set of applicable chassis and corresponding plasmids to improve recombinant expression level, expecting to be used for difficult-to-express proteins.
Hb Levels and Sex Differences in Relation to Short-Term Outcomes in Patients With Acute Myocardial Infarction
Authors: Pei Junyu , Wang Xiaopu , Chen Pengfei , Zheng Keyang , Hu Xinqun
Published: July 2021

Background: Women had worse outcomes after acute myocardial infarction (AMI), and physiologically, women had lower hemoglobin values. We examined whether there were sex-related differences in the relationship between hemoglobin levels and adverse outcomes in patients with acute myocardial infarction.

Method: We conducted a post-hoc analysis of data from the Acute Coronary Syndrome Quality Improvement in Kerala (ACS-QUIK) Study. We explored the relationship between baseline hemoglobin level and 30-days adverse outcomes by logistic regression model, generalized additive model (GAM) and two-piecewise linear regression model. We used multiple imputation, based on five replications and a chained equation approach method in the R multiple imputation procedure, to account for missing data. The primary outcome were 30-day major adverse cardiovascular events (MACEs) defined as death, reinfarction, stroke, and major bleeding. The secondary outcomes were 30-day major bleeding, 30-day stroke and 30-day cardiovascular death (CVD death).

Results: Twenty thousand, five hundred fifty-nine patients with AMI were included in our analysis. Baseline hemoglobin level was associated with major bleeding [OR: 0.74, 95%CI (0.60, 0.92) P < 0.01], CVD death [OR: 0.94, 95%CI (0.90, 0.99) P < 0.01], and MACEs [OR: 0.95, 95%CI (0.92, 0.99) P < 0.01]. There was no significant relationship between baseline hemoglobin level and stroke incidence in both men [OR: 1.02, 95%CI (0.90, 1.14) P = 0.77] and women [OR: 1.15, 95%CI (0.96, 1.37) P = 0.18]. Baseline hemoglobin level was associated with major bleeding [OR: 0.71, 95%CI (0.58, 0.85) P < 0.01] in male patients, however we did not find the same relationship in female patients [OR: 0.89, 95%CI (0.56, 1.41) P = 0.61]. GAM and two-piecewise linear regression model showed the relationships of hemoglobin level with major bleeding, CVD death, and MACEs were non-linear (non-linear P < 0.05), and the threshold value were 13, 14.8, and 14.3 g/dL for MACEs and CVD death, respectively.

Conclusion: Baseline hemoglobin level was one of the independent predictors of prognosis in South Asia patients with acute myocardial infarction. Moreover, its impact on prognosis was largely different depending on the patients' sex.
Cardiomyocyte Protection by Hibernating Brown Bear Serum: Toward the Identification of New Protective Molecules Against Myocardial Infarction
Authors: Givre Lucas , Crola Da Silva Claire , Swenson Jon E. , Arnemo Jon M. , Gauquelin-Koch Guillemette , Bertile Fabrice , Lefai Etienne , Gomez Ludovic
Published: July 2021

Ischemic heart disease remains one of the leading causes of death worldwide. Despite intensive research on the treatment of acute myocardial infarction, no effective therapy has shown clinical success. Therefore, novel therapeutic strategies are required to protect the heart from reperfusion injury. Interestingly, despite physical inactivity during hibernation, brown bears (Ursus arctos) cope with cardiovascular physiological conditions that would be detrimental to humans. We hypothesized that bear serum might contain circulating factors that could provide protection against cell injury. In this study, we sought to determine whether addition of bear serum might improve cardiomyocyte survival following hypoxia–reoxygenation. Isolated mouse cardiomyocytes underwent 45 min of hypoxia followed by reoxygenation. At the onset of reoxygenation, cells received fetal bovine serum (FBS; positive control), summer (SBS) or winter bear serum (WBS), or adult serums of other species, as indicated. After 2 h of reoxygenation, propidium iodide staining was used to evaluate cell viability by flow cytometry. Whereas, 0.5% SBS tended to decrease reperfusion injury, 0.5% WBS significantly reduced cell death, averaging 74.04 ± 7.06% vs. 79.20 ± 6.53% in the FBS group. This cardioprotective effect was lost at 0.1%, became toxic above 5%, and was specific to the bear. Our results showed that bear serum exerts a therapeutic effect with an efficacy threshold, an optimal dose, and a toxic effect on cardiomyocyte viability after hypoxia–reoxygenation. Therefore, the bear serum may be a potential source for identifying new therapeutic molecules to fight against myocardial reperfusion injury and cell death in general.
Modeling of Tectonic-Thermal Evolution of Cretaceous Qingshankou Shale in the Changling Sag, Southern Songliao Basin, NE China
Authors: Liu Yuchen , Liu Bo , Cheng LiJuan , Xing Jilin , Tian Shansi , Huang Saipeng , Dong Suying
Published: July 2021

A series of significant shale oil discoveries have been made recently in the Upper Cretaceous Qingshankou Formation in the Songliao Basin, providing a new resource target for shale oil exploration in Northeast China. In this context, an understanding of the tectonic-thermal evolution and maturation history of the Qingshankou Formation is of great significance for shale oil exploration and evaluation. In this study, the thermal history of the Qingshankou Formation since the Late Cretaceous was reconstructed using the paleothermal indicator method. The results indicate that two stages of thermal evolution exist in the southern part of the Songliao Basin: 1) the gradual heating stage during the Late Cretaceous; the heat flow gradually increases during this period and reaches a maximum heat flow value at the end of the Cretaceous. 2) The decline stage since the Neogene; the tectonic activity is relatively stable and the geothermal heat flow is gradually reduced, and the present-day heat flow ranges from 60.1 to 100.7 mW/m2, with an average of 78.2 mW/m2. In addition, the maturity history of the organic-rich shale was reconstructed based on the new thermal history. The Cretaceous Qingshankou shales underwent deep burial thermal metamorphism at the end of the Cretaceous, whereas thermal has faded since the Neogene. The hydrocarbon generation and migration since the Late Cretaceous period of K2qn1 were modeled based on the maturity model. Two main cooling events took place in the late Nenjiang period and the late Mingshui period in the Changling sag. These two tectonic events controlled the structural style and the formation of shale oil reservoirs in the southern Songliao Basin.
Analysis of Hydrogen Gas Injection at Various Compositions in an Existing Natural Gas Pipeline
Authors: Liu Jingxuan , Teng Lin , Liu Bin , Han Peng , Li Weidong
Published: July 2021

The lack of hydrogen (H2) transportation infrastructure restricts the development of the H2 industry. Owing to the high investment of building specific facilities, using existing natural gas (NG) pipelines to transport a blend of H2 and NG (H2NG) is a viable means of transportation and approach for large-scale long-time storage. However, variation in the thermo-physical properties of an H2NG blend will impact the performance of pipeline appliances. To address the gaps in H2 transmission via an NG system in the context of energy consumption, in the present paper, a one-dimensional pipeline model is proposed to predict the blended flow in a real existing pipeline (Shan–Jing I, China). The data of NG components were derived from real gas fields. Furthermore, the influence of H2 fractions on pipeline energy coefficient and the layout of pressurization stations are comprehensively analyzed. In addition, the case of intermediate gas injection is investigated, and the effects of injection positions are studied. This study serves as a useful reference for the design of an H2NG pipeline system. The present study reveals that with the increasing in H2 fraction, the distance between pressure stations increases. Furthermore, when the arrangement of original pressure stations is maintained, overpressure occur. Intermediate gas injection results in the inlet pressure of subsequent pressurization stations reducing. Using existing pipeline network to transport H2NG, it is necessary to make appropriate adjustment.
Fault Location Scheme for Abnormal Grounding Point in Isolated Ground Wire of Large-Scale Clean Energy Transmission
Authors: Wang Yunlong , Chen Nuo , Ma Xiangnan , Yang Zongzhang
Published: July 2021

There is a large number of grounding switches along the isolated ground wire for the de-icing in the large-scale wind farm. If any of these grounding switches are left open by accident, this can create an unexpected abnormal grounding point in the isolated ground wire. Based on the analysis of the output power of de-icing devices, the output power of different poles can be applied for the abnormal grounding point fault location. Since the rise of output current to the rated current of de-icing devices requires a long time to build up, the protective relay may lock the de-icing device before the output current reaches the rated current. Thus, the ratio of output energy of two poles can be selected to locate the abnormal grounding point. This study verified this location method by conducting a large number of simulations.
Effects of Climate and Atmospheric Nitrogen Deposition on Early to Mid-Term Stage Litter Decomposition Across Biomes
Authors: Kwon TaeOh , Shibata Hideaki , Kepfer-Rojas Sebastian , Schmidt Inger K. , Larsen Klaus S. , Beier Claus , Berg Björn , Verheyen Kris , Lamarque Jean-Francois , Hagedorn Frank , Eisenhauer Nico , Djukic Ika ,   TeaComposition Network
Published: July 2021

Litter decomposition is a key process for carbon and nutrient cycling in terrestrial ecosystems and is mainly controlled by environmental conditions, substrate quantity and quality as well as microbial community abundance and composition. In particular, the effects of climate and atmospheric nitrogen (N) deposition on litter decomposition and its temporal dynamics are of significant importance, since their effects might change over the course of the decomposition process. Within the TeaComposition initiative, we incubated Green and Rooibos teas at 524 sites across nine biomes. We assessed how macroclimate and atmospheric inorganic N deposition under current and predicted scenarios (RCP 2.6, RCP 8.5) might affect litter mass loss measured after 3 and 12 months. Our study shows that the early to mid-term mass loss at the global scale was affected predominantly by litter quality (explaining 73% and 62% of the total variance after 3 and 12 months, respectively) followed by climate and N deposition. The effects of climate were not litter-specific and became increasingly significant as decomposition progressed, with MAP explaining 2% and MAT 4% of the variation after 12 months of incubation. The effect of N deposition was litter-specific, and significant only for 12-month decomposition of Rooibos tea at the global scale. However, in the temperate biome where atmospheric N deposition rates are relatively high, the 12-month mass loss of Green and Rooibos teas decreased significantly with increasing N deposition, explaining 9.5% and 1.1% of the variance, respectively. The expected changes in macroclimate and N deposition at the global scale by the end of this century are estimated to increase the 12-month mass loss of easily decomposable litter by 1.1–3.5% and of the more stable substrates by 3.8–10.6%, relative to current mass loss. In contrast, expected changes in atmospheric N deposition will decrease the mid-term mass loss of high-quality litter by 1.4–2.2% and that of low-quality litter by 0.9–1.5% in the temperate biome. Our results suggest that projected increases in N deposition may have the capacity to dampen the climate-driven increases in litter decomposition depending on the biome and decomposition stage of substrate.
Genotypic and Phenotypic Characteristics of 29 Patients With Rare Types of Osteogenesis Imperfecta: Average 5 Years of Follow-Up
Authors: Xi Lei , Zhang Hao , Zhang Zhen-Lin
Published: July 2021

Osteogenesis imperfecta (OI) is a rare genetic disorder characterized by bone fragility and abnormal connective tissue. Ninety percent of OI patients are caused by two mutations of COL1A1 and COL1A2, and more investigation was needed to better understand the rare types of OI. We followed up 29 patients with rare types of OI for an average of 5.4 years, and genotype, height, bone mineral density (BMD), blood biochemical indexes, misdiagnosis, and fracture were recorded. IFITM5 gene mutation was found in 18 patients (62.1%), which represents the most common pathogenic gene of rare types of OI in Chinese population. Thirteen cases had once been misdiagnosed, and the initial misdiagnosis rate was 44.8% (13/29). The higher misdiagnosis rate should be paid attention to by clinicians and healthcare providers, and we also give corresponding suggestions. Compared with the non-bisphosphonate treatment group, patients treated with bisphosphonates had higher lumbar spine BMD, fewer fractures, and lower levels of β-CTX and osteocalcin. However, there was no significant difference between OI type V patients and non-type V patients. Our study enriched the knowledge of genotype and phenotype characteristics of OI patients with rare types and bisphosphonate therapy.
Comprehensive Analysis of the Value of SMYD Family Members in the Prognosis and Immune Infiltration of Malignant Digestive System Tumors
Authors: Liu Donghui , Wang Xuyao , Shi Enhong , Wang Liru , Nie Minghao , Li Long , Jiang Qingxin , Kong Pengyu , Shi Shuai , Wang Chao , Yan Sen , Qin Zhihui , Zhao Shuang
Published: July 2021

Background

The SET and MYND domain-containing (SMYD) gene family comprises a set of genes encoding lysine methyltransferases. This study aimed to clarify the relationship between the expression levels of SMYD family members and the prognosis and immune infiltration of malignant tumors of the digestive system.

Methods

The Oncomine, Ualcan, Kaplan–Meier Plotter, cBioPortal, Metascape, and TIMER databases and tools were used to analyze the correlation of SMYD family mRNA expression, clinical stage, TP53 mutation status, prognostic value, gene mutation, and immune infiltration in patients with esophageal carcinoma (ESCA), liver hepatocellular carcinoma (LIHC), and stomach adenocarcinoma (STAD).

Results

In ESCA, the mRNA expression of SMYD2/3/4/5 was significantly correlated with the incidence rate, that of SMYD2/3 with the clinical stage, that of SMYD2/3/4/5 with TP53 mutation status, that of SMYD2/4/5 with overall survival (OS), and that of SMYD1/2/3/4 with relapse-free survival (RFS). In LIHC, the mRNA expression of SMYD1/2/3/4/5 was significantly correlated with the incidence rate, that of SMYD2/4/5 with the clinical stage, that of SMYD3/5 with TP53 mutation status, that of SMYD2/3/4/5 with OS, and that of SMYD3/5 with RFS. In STAD, the mRNA expression of SMYD2/3/4/5 was significantly correlated with the incidence rate, that of SMYD1/4 with the clinical stage, that of SMYD1/2/3/5 with TP53 mutation status, that of SMYD1/3/4 with OS, and that of SMYD1/3 with RFS. Furthermore, the function of SMYD family mutation-related genes in ESCA, LIHC, and STAD patients was mainly related to pathways, such as mitochondrial gene expression, mitochondrial matrix, and mitochondrial translation. The expression of SMYD family genes was significantly correlated with the infiltration of six immune cell types and eight types of immune check sites.

Conclusion

SMYD family genes are differentially expressed and frequently mutated in malignant tumors of the digestive system (ESCA, LIHC, and gastric cancer). They are potential markers for prognostic prediction and have important significance in immunity and targeted therapy.
LncRNATUG1 Facilitates Th2 Cell Differentiation by Targeting the miR-29c/B7-H3 Axis on Macrophages
Authors: Sun Huiming , Wang Ting , Zhang Weili , Dong Heting , Gu Wenjing , Huang Li , Yan Yongdong , Zhu Canhong , Chen Zhengrong
Published: July 2021

The role of long non-coding RNAs (lncRNA) in asthma remains unclear. In this study, we examined the role of long non-coding RNA taurine upregulated 1 (lncRNA TUG1) in asthma. We found that lncRNA TUG1 is one of the differentially expressed lncRNAs in the monocytes of asthmatic children and is associated with Th cell differentiation. LncRNA TUG1 and miR-29c are mainly distributed in the cytoplasm of macrophages. Our data suggested that lncRNA TUG1 increased in macrophages stimulated by House Dust Mite in a dose-dependent manner. Using loss- and gain of function strategy, we found that miR-29c might regulate Th2 cell differentiation by directly targeting co-stimulatory molecule B7-H3. Furthermore, down-regulation of lncRNA TUG1 decreased the level of GATA3 in CD4+T cells and was associated with miR-29c/B7-H3 axis. Moreover, the dual-luciferase reporter assay confirmed that lncRNA TUG1 serves as a competing endogenous RNA to sponge miR-29c. According to the rescue experiment, lncRNA TUG1 regulated Th2 cell differentiation via miR-29c. These data suggest that lncRNA TUG1 in macrophages regulates Th2 cell differentiation via miR-29c/B7-H3 axis.
Targeting Tristetraprolin Expression or Functional Activity Regulates Inflammatory Response Induced by MSU Crystals
Authors: lv Linxi , Qin Ting , Huang Qiushi , Jiang Hui , Chen Feng , Long Fan , Ren Long , Liu Jianpin , Xie Yongen , Zeng Mei
Published: July 2021

The RNA-binding protein tristetraprolin (TTP) is an anti-inflammatory factor that prompts the mRNA decay of target mRNAs and is involved in inflammatory diseases such as rheumatoid arthritis (RA). TTP is regulated by phosphorylation, and protein phosphatase 2A (PP2A) can dephosphorylate TTP to activate its mRNA-degrading function. Some small molecules can enhance PP2A activation. Short interfering RNA (siRNA) targeting TTP expression or PP2A agonist (Arctigenin) was administered to monosodium urate (MSU) crystal-induced J774A.1 cells, and the expression of inflammatory related genes was detected by RT-PCR and Western blot assays. The effects of Arctigenin in mouse models of acute inflammation induced by MSU crystals, including peritonitis and arthritis, were evaluated. The data indicated that TTP expression levels and endogenous PP2A activity were increased in MSU-crystal treated J774A.1 cells. TTP knockdown exacerbated inflammation-related genes expression and NLRP3 inflammasome activation. However, PP2A agonist treatment (Arctigenin) suppressed MSU crystal-induced inflammation in J774A.1 cells. Arctigenin also relieved mitochondrial reactive oxygen species (mtROS) production and improved lysosomal membrane permeability in MSU crystal-treated J774A.1 cells. Moreover, TTP knockdown reversed the anti-inflammatory and antioxidant effects of Arctigenin. Oral administration of Arctigenin significantly alleviated foot pad swelling, the number of inflammatory cells in peritoneal lavage fluids and the production of IL-1β in the mouse model of inflammation induced by MSU crystals. Collectively, these data imply that targeting TTP expression or functional activity may provide a potential therapeutic strategy for inflammation caused by MSU crystals.
Case Report and Review of the Literature: Bullous Skin Eruption After the Booster-Dose of Influenza Vaccine in a Pediatric Patient With Polymorphic Maculopapular Cutaneous Mastocytosis
Authors: Sarcina Davide , Giovannini Mattia , Oranges Teresa , Barni Simona , Pedaci Fausto Andrea , Liccioli Giulia , Canessa Clementina , Sarti Lucrezia , Lodi Lorenzo , Filippeschi Cesare , Azzari Chiara , Ricci Silvia , Mori Francesca
Published: July 2021

Vaccination is a well-known trigger for mast cell degranulation in subjects affected by mastocytosis. Nevertheless, there is no exact standardized protocol to prevent a possible reaction after a vaccine injection, especially for patients who have already presented a previous vaccine-related adverse event, considering that these patients frequently tolerate future vaccine doses. For this reason, we aim to share our experience at Meyer Children’s University Hospital in Florence to raise awareness on the potential risk for future vaccinations and to discuss the valuable therapeutic strategies intended to prevent them, taking into account what is proposed by experts in literature. We describe the case of an 18-month-old female affected by a polymorphic variant of maculopapular cutaneous mastocytosis that presented an extensive bullous cutaneous reaction 24 hours after the second dose (booster dose) of inactivated-tetravalent influenza vaccine, treated with a single dose of oral corticosteroid therapy with betamethasone (0.1 mg/kg) and an oral antihistamine therapy with oxatomide (1 mg/kg/daily) for a week, until resolution. To the best of our knowledge, in the literature, no documented case of reaction to influenza vaccine in maculopapular cutaneous mastocytosis is described. Subsequently, the patient started a background therapy with ketotifen daily (0.05 mg/kg twice daily), a non-competitive H1-antihistamine, and a mast cell stabilizer (dual activity). A non-standardized pharmacological premedication protocol with an H1-receptor antagonist (oxatomide, 0.5 mg/kg) administered 12 hours before the immunizations, and a single dose of betamethasone (0.05 mg/kg) together with another dose of oxatomide (0.5 mg/kg) administered 2 hours before the injections was followed to make it possible for the patient to continue with the scheduled vaccinations. Indeed, no reactions were subsequently reported. Thus, in our experience, a background therapy with ketotifen associated with a premedication protocol made by two doses of oxatomide and a single dose of betamethasone was helpful to make possible the execution of the other vaccines. We suggest how in these children, it could be considered the idea of taking precaution when vaccination is planned, regardless of the kind of vaccine and if a dose of the same vaccine was previously received. However, international consensus needs to be reached to manage vaccinations in children with mastocytosis and previous adverse reactions to vaccines.
Mechanism of Immunoregulatory Properties of Vasoactive Intestinal Peptide in the K/BxN Mice Model of Autoimmune Arthritis
Authors: Leceta Javier , Garin Marina I. , Conde Carmen
Published: July 2021

The K/BxN mouse model of rheumatoid arthritis (RA) closely resembles the human disease. In this model, arthritis results from activation of autoreactive KRN T cells recognizing the glycolytic enzyme glucose-6-phosphate isomerase (GPI) autoantigen, which provides help to GPI-specific B cells, resulting in the production of pathogenic anti-GPI antibodies that ultimately leads to arthritis symptoms from 4 weeks of age. Vasoactive intestinal peptide (VIP) is a neuropeptide broadly distributed in the central and peripheral nervous system that is also expressed in lymphocytes and other immune cell types. VIP is a modulator of innate and adaptive immunity, showing anti-inflammatory and immunoregulatory properties. Basically, this neuropeptide promotes a shift in the Th1/Th2 balance and enhances dedifferentiation of T regulatory cells (Treg). It has demonstrated its therapeutic effects on the collagen-induced arthritis (CIA) mouse model of RA. In the present hypothesis and theory article, we propose that the immunoregulatory properties of VIP may be due likely to the inhibition of T cell plasticity toward non-classic Th1 cells and an enhanced follicular regulatory T cells (Tfr) activity. The consequences of these regulatory properties are the reduction of systemic pathogenic antibody titers.
NPM1 Is a Prognostic Biomarker Involved in Immune Infiltration of Lung Adenocarcinoma and Associated With m6A Modification and Glycolysis
Authors: Liu Xu-Sheng , Zhou Lu-Meng , Yuan Ling-Ling , Gao Yan , Kui Xue-Yan , Liu Xiao-Yu , Pei Zhi-Jun
Published: July 2021

Background

Overexpression of NPM1 can promote the growth and proliferation of various tumor cells. However, there are few studies on the comprehensive analysis of NPM1 in lung adenocarcinoma (LUAD).

Methods

TCGA and GEO data sets were used to analyze the expression of NPM1 in LUAD and clinicopathological analysis. The GO/KEGG enrichment analysis of NPM1 co-expression and gene set enrichment analysis (GSEA) were performed using R software package. The relationship between NPM1 expression and LUAD immune infiltration was analyzed using TIMER, GEPIA database and TCGA data sets, and the relationship between NPM1 expression level and LUAD m6A modification and glycolysis was analyzed using TCGA and GEO data sets.

Results

NPM1 was overexpressed in a variety of tumors including LUAD, and the ROC curve showed that NPM1 had a certain accuracy in predicting the outcome of tumors and normal samples. The expression level of NPM1 in LUAD is significantly related to tumor stage and prognosis. The GO/KEGG enrichment analysis indicated that NPM1 was closely related to translational initiation, ribosome, structural constituent of ribosome, ribosome, Parkinson disease, and RNA transport. GSEA showed that the main enrichment pathway of NPM1-related differential genes was mainly related to mTORC1 mediated signaling, p53 hypoxia pathway, signaling by EGFR in cancer, antigen activates B cell receptor BCR leading to generation of second messengers, aerobic glycolysis and methylation pathways. The analysis of TIMER, GEPIA database and TCGA data sets showed that the expression level of NPM1 was negatively correlated with B cells and NK cells. The TCGA and GEO data sets analysis indicated that the NPM1 expression was significantly correlated with one m6A modifier related gene (HNRNPC) and five glycolysis related genes (ENO1, HK2, LDHA, LDHB and SLC2A1).

Conclusion

NPM1 is a prognostic biomarker involved in immune infiltration of LUAD and associated with m6A modification and glycolysis. NPM1 can be used as an effective target for diagnosis and treatment of LUAD.
Integrating Coral Restoration Data With a Novel Coral Sample Registry
Authors: Moura Amelia , Beck Brian , Duffey Renee , McEachron Lucas , Miller Margaret , Moore Jennifer , Moulding Alison , Winters R. Scott
Published: July 2021

In the past decade, the field of coral reef restoration has experienced a proliferation of data detailing the source, genetics, and performance of coral strains used in research and restoration. Resource managers track the multitude of permits, species, restoration locations, and performance across multiple stakeholders while researchers generate large data sets and data pipelines detailing the genetic, genomic, and phenotypic variants of corals. Restoration practitioners, in turn, maintain records on fragment collection, genet performance, outplanting location and survivorship. While each data set is important in its own right, collectively they can provide deeper insights into coral biology and better guide coral restoration endeavors – unfortunately, current data sets are siloed with limited ability to cross-mine information for deeper insights and hypothesis testing. Herein we present the Coral Sample Registry (CSR), an online resource that establishes the first step in integrating diverse coral restoration data sets. Developed in collaboration with academia, management agencies, and restoration practitioners in the South Florida area, the CSR centralizes information on sample collection events by issuing a unique accession number to each entry. Accession numbers can then be incorporated into existing and future data structures. Each accession number is unique and corresponds to a specific collection event of coral tissue, whether for research, archiving, or restoration purposes. As such the accession number can serve as the key to unlock the diversity of information related to that sample’s provenance and characteristics across any and all data structures that include the accession number field. The CSR is open-source and freely available to users, designed to be suitable for all coral species in all geographic regions. Our goal is that this resource will be adopted by researchers, restoration practitioners, and managers to efficiently track coral samples through all data structures and thus enable the unlocking of a broader array of insights.
Monitoring Non-indigenous Species in Port Habitats: First Application of a Standardized North American Protocol in the Mediterranean Sea
Authors: Tamburini Marco , Keppel Erica , Marchini Agnese , Repetto Michele F. , Ruiz Gregory M. , Ferrario Jasmine , Occhipinti-Ambrogi Anna
Published: July 2021

Baseline port monitoring for fouling communities is an essential tool to assess non-indigenous species (NIS) introduction and spread, but a standardized and coordinated method among Mediterranean and European countries has not yet been adopted. In this context, it is important to test monitoring protocols that allow for the collection of standardized and directly comparable data, replicated across time and space. Here, for the first time in the Mediterranean Sea, we tested a standardized protocol developed by the Smithsonian Environmental Research Center (SERC) and used now in several countries. The 3-year monitoring survey (2018–2020) was conducted in the Gulf of La Spezia (Ligurian Sea, Italy), with the deployment of a total of 50 PVC panels per year in five different sites (a commercial harbor, three marinas and a site in the proximity of a shellfish farm). A total of 79 taxa were identified, including 11 NIS, ranging from zero to seven NIS for each panel. In comparison with previous surveys, new NIS arrivals were observed in the Gulf of La Spezia: Botrylloides cf. niger, Branchiomma sp., Branchiomma luctuosum, Paraleucilla magna, and Watersipora arcuata. At the end of the 3-year monitoring, mean richness? and percent cover of NIS were measured, and both measures differed across the monitoring sites, with higher values in two marinas and in the commercial harbor. Among years, richness of NIS was relatively stable at each monitoring site. The structure of the fouling was influenced more by native and cryptogenic species than by NIS. Moreover, among the monitoring sites, the density of artificial structures was not a reliable predictor or proxy for local NIS abundance. This first application of the SERC method in the Mediterranean Sea, demonstrates both pros and cons, including the detection of new NIS reported here. Further direct comparisons with other NIS monitoring tools are recommended, and additional tests to assess its effectiveness in this biogeographical area are encouraged. A broader application of this and other standard methods across temporal and spatial scales in the Mediterranean basin should be implemented, providing critical data needed to assess changes in the structure of fouling communities.
Thiopurines in Inflammatory Bowel Disease. How to Optimize Thiopurines in the Biologic Era?
Authors: Gargallo-Puyuelo Carla J. , Laredo Viviana , Gomollón Fernando
Published: July 2021

Thiopurines have been a cornerstone in the treatment of inflammatory bowel disease (IBD). Although they have been used for more than 50 years, there are still some unsolved issues about their efficacy and, also, some safety concerns, mainly the risk of myelosuppression and life-threatening lymphoproliferative disorders. Furthermore, the development of biological therapy raises the question whether there is still a role for thiopurines in the IBD treatment algorithm. On the other hand, limited cost and wide availability make thiopurines a reasonable option in settings of limited resources and increasing prevalence of IBD. In fact, there is a growing interest in optimizing thiopurine therapy, since pharmacogenomic findings suggest that a personalized approach based on the genotyping of some molecules involved in its metabolism could be useful to prevent side effects. Polymorphisms of thiopurine methyltransferase enzyme (TPMT) that result in low enzymatic activity have been associated with an increased risk of myelotoxicity, especially in Caucasians; however, in Asians it is assumed that the variants of nudix hydrolase 15 (NUDT15) are more relevant in the development of toxicity. Age is also important, since in elderly patients the risk of complications seems to be increased. Moreover, the primo-infection of Epstein Barr virus and cytomegalovirus under thiopurine treatment has been associated with severe lymphoproliferative disorders. In addition to assessing individual characteristics that may influence thiopurines treatment outcomes, this review also discusses other strategies to optimize the therapy. Low-dose thiopurines combined with allopurinol can be used in hypermethylators and in thiopurine-related hepatotoxicity. The measurement of metabolites could be useful to assess compliance, identify patients at risk of adverse events and also facilitating the management of refractory patients. Thioguanine is also a rescue therapy in patients with toxicity related to conventional thiopurine therapy. Finally, the current indications for thiopurines in monotherapy or in combination with biologics, as well as the optimal duration of treatment, are also reviewed.
Routine Hematological Parameters May Be Predictors of COVID-19 Severity
Authors: Szklanna Paulina B. , Altaie Haidar , Comer Shane P. , Cullivan Sarah , Kelliher Sarah , Weiss Luisa , Curran John , Dowling Emmet , O'Reilly Katherine M. A. , Cotter Aoife G. , Marsh Brian , Gaine Sean , Power Nick , Lennon Áine , McCullagh Brian , Ní Áinle Fionnuala , Kevane Barry , Maguire Patricia B.
Published: July 2021

To date, coronavirus disease 2019 (COVID-19) has affected over 100 million people globally. COVID-19 can present with a variety of different symptoms leading to manifestation of disease ranging from mild cases to a life-threatening condition requiring critical care-level support. At present, a rapid prediction of disease severity and critical care requirement in COVID-19 patients, in early stages of disease, remains an unmet challenge. Therefore, we assessed whether parameters from a routine clinical hematology workup, at the time of hospital admission, can be valuable predictors of COVID-19 severity and the requirement for critical care. Hematological data from the day of hospital admission (day of positive COVID-19 test) for patients with severe COVID-19 disease (requiring critical care during illness) and patients with non-severe disease (not requiring critical care) were acquired. The data were amalgamated and cleaned and modeling was performed. Using a decision tree model, we demonstrated that routine clinical hematology parameters are important predictors of COVID-19 severity. This proof-of-concept study shows that a combination of activated partial thromboplastin time, white cell count-to-neutrophil ratio, and platelet count can predict subsequent severity of COVID-19 with high sensitivity and specificity (area under ROC 0.9956) at the time of the patient's hospital admission. These data, pending further validation, indicate that a decision tree model with hematological parameters could potentially form the basis for a rapid risk stratification tool that predicts COVID-19 severity in hospitalized patients.
Antibodies Can Last for More Than 1 Year After SARS-CoV-2 Infection: A Follow-Up Study From Survivors of COVID-19
Authors: Xiao Kaihu , Yang Haiyan , Liu Bin , Pang Xiaohua , Du Jianlin , Liu Mengqi , Liu Yajie , Jing Xiaodong , Chen Jing , Deng Songbai , Zhou Zheng , Du Jun , Yin Li , Yan Yuling , Mou Huaming , She Qiang
Published: July 2021

Background: COVID-19 is a global pandemic. The prevention of SARS-CoV-2 infection and the rehabilitation of survivors are currently the most urgent tasks. However, after patients with COVID-19 are discharged from the hospital, how long the antibodies persist, whether the lung lesions can be completely absorbed, and whether cardiopulmonary abnormalities exist remain unclear.

Methods: A total of 56 COVID-19 survivors were followed up for 12 months, with examinations including serum virus-specific antibodies, chest CT, and cardiopulmonary exercise testing.

Results: The IgG titer of the COVID-19 survivors decreased gradually, especially in the first 6 months after discharge. At 6 and 12 months after discharge, the IgG titer decreased by 68.9 and 86.0%, respectively. The IgG titer in patients with severe disease was higher than that in patients with non-severe disease at each time point, but the difference did not reach statistical significance. Among the patients, 11.8% were IgG negative up to 12 months after discharge. Chest CT scans showed that at 3 and 10 months after discharge, the lung opacity had decreased by 91.9 and 95.5%, respectively, as compared with that at admission. 10 months after discharge, 12.5% of the patients had an opacity percentage >1%, and 18.8% of patients had pulmonary fibrosis (38.5% in the severe group and 5.3% in the non-severe group, P < 0.001). Cardiopulmonary exercise testing showed that 22.9% of patients had FEV1/FVC%Pred <92%, 17.1% of patients had FEV1%Pred <80%, 20.0% of patients had a VO2 AT <14 mlO2/kg/min, and 22.9% of patients had a VE/VCO2 slope >30%.

Conclusions: IgG antibodies in most patients with COVID-19 can last for at least 12 months after discharge. The IgG titers decreased significantly in the first 6 months and remained stable in the following 6 months. The lung lesions of most patients with COVID-19 can be absorbed without sequelae, and a few patients in severe condition are more likely to develop pulmonary fibrosis. Approximately one-fifth of the patients had cardiopulmonary dysfunction 6 months after discharge.
The Long-Term Effects of Using Phosphate-Solubilizing Bacteria and Photosynthetic Bacteria as Biofertilizers on Peanut Yield and Soil Bacteria Community
Authors: Wang Yiming , Peng Shuang , Hua Qingqing , Qiu Chongwen , Wu Pan , Liu Xiaoli , Lin Xiangui
Published: July 2021

Microbial inoculation is a promising strategy to improve crop yields and reduce the use of chemical fertilizers, thereby creating environment-friendly agriculture. In this study, the long-term (5 years) effects of a phosphate-solubilizing bacterium Burkholderia cepacia ISOP5, a purple non-sulfur bacterium Rhodopseudomonas palustris ISP-1, and a mixed inoculation of these two bacteria (MB) on peanut yield, soil microbial community structure, and microbial metabolic functions were evaluated in a field experiment. After 5 years of inoculation, total peanut yield with B. cepacia ISOP5, R. palustris ISP-1, and MB treatments increased by 8.1%, 12.5%, and 19.5%, respectively. The treatments also significantly promoted the absorption of N and increased the protein content in peanut seeds. Nutrient content also increased to some extent in the bacteria-inoculum-treated soil. However, bacterial community diversity and richness were not significantly affected by bacterial inoculums, and only minor changes occurred in the bacterial community composition. Functional prediction revealed that bacterial inoculums reduced the relative abundance of those genes associated with P uptake and transport as well as increased the abundance of genes associated with inorganic P solubilization and organic P mineralization. Bacterial inoculums also increased the total relative abundance of genes associated with N metabolism. In addition to developing sustainable and eco-friendly agricultural practice, crop inoculation with B. cepacia ISOP5 and R. palustris ISP-1 would improve soil fertility, enhance microbial metabolic activity, and increase crop yield.