bluuebunny/crossref_metadata_2025 huggingface dataset:
IL-1 Family Antagonists in Mouse and Human Skin Inflammation
Authors: Martin Praxedis , Goldstein Jérémie D. , Mermoud Loïc , Diaz-Barreiro Alejandro , Palmer Gaby
Published: March 2021

Interleukin (IL)-1 family cytokines initiate inflammatory responses, and shape innate and adaptive immunity. They play important roles in host defense, but excessive immune activation can also lead to the development of chronic inflammatory diseases. Dysregulated IL-1 family signaling is observed in a variety of skin disorders. In particular, IL-1 family cytokines have been linked to the pathogenesis of psoriasis and atopic dermatitis. The biological activity of pro-inflammatory IL-1 family agonists is controlled by the natural receptor antagonists IL-1Ra and IL-36Ra, as well as by the regulatory cytokines IL-37 and IL-38. These four anti-inflammatory IL-1 family members are constitutively and highly expressed at steady state in the epidermis, where keratinocytes are a major producing cell type. In this review, we provide an overview of the current knowledge concerning their regulatory roles in skin biology and inflammation and their therapeutic potential in human inflammatory skin diseases. We further highlight some common misunderstandings and less well-known observations, which persist in the field despite recent extensive interest for these cytokines.
The Interplay Between Chromatin Architecture and Lineage-Specific Transcription Factors and the Regulation of Rag Gene Expression
Authors: Miyazaki Kazuko , Miyazaki Masaki
Published: March 2021

Cell type-specific gene expression is driven through the interplay between lineage-specific transcription factors (TFs) and the chromatin architecture, such as topologically associating domains (TADs), and enhancer-promoter interactions. To elucidate the molecular mechanisms of the cell fate decisions and cell type-specific functions, it is important to understand the interplay between chromatin architectures and TFs. Among enhancers, super-enhancers (SEs) play key roles in establishing cell identity. Adaptive immunity depends on the RAG-mediated assembly of antigen recognition receptors. Hence, regulation of theRag1andRag2(Rag1/2) genes is a hallmark of adaptive lymphoid lineage commitment. Here, we review the current knowledge of 3D genome organization, SE formation, andRag1/2gene regulation during B cell and T cell differentiation.
Future Changes in Oceanography and Biogeochemistry Along the Canadian Pacific Continental Margin
Authors: Holdsworth Amber M. , Zhai Li , Lu Youyu , Christian James R.
Published: March 2021

Model projections of ocean circulation and biogeochemistry are used to investigate large scale climate changes under moderate mitigation (RCP 4.5) and high emissions (RCP 8.5) scenarios along the continental shelf of the Canadian Pacific Coast. To reduce computational cost, an approach for dynamical downscaling of climate projections was developed that uses atmospheric climatologies with augmented winds to simulate historical (1986–2005) and future (2046–2065) periods separately. The two simulations differ in initial and lateral open boundary conditions. For each simulation, the daily climatology of surface winds in the driving model was augmented with high-frequency variability from an atmospheric reanalysis product. The “time-slice” approach was able to reproduce the observed climate state for the historical period. Sensitivity tests confirmed that the high frequency wind variability plays an essential role in freshwater distribution in this region. Projections suggest that sea surface temperature will increase by 1.8–2.4°C and surface salinity will decrease between −0.08 and −0.23 depending on whether a moderate or high emissions scenario is used. Stratification increases throughout the region and there is some evidence of nutrient limitation near the surface. Primary production and phytoplankton productivity (chlorophyll) also increase. Density surfaces are relocated deeper in the water column and this change is mainly driven by surface heating and freshening. Changes in saturation state are mainly due to anthropogenic CO2with minor contributions from solubility, remineralization and advection. There is little difference between RCP 4.5 and RCP 8.5 with regard to projections of deoxygenation and acidification. The depths of the aragonite saturation state and the oxygen minimum zone are projected to become shallower by ≃ 100 and ≃ 75 m respectively. Extreme states of temperature, oxygen and acidification are projected to become more frequent and more extreme, with the frequency of occurrence of[O2]<60 mmolm-3expected to approximately double under either scenario.
Elastically Graded Titanium Alloy Produced by Mechanical Surface Deformation
Authors: Delannoy Stéphanie , Baïz Sarah , Laheurte Pascal , Jordan Laurence , Prima Frédéric
Published: March 2021

The objective of this study was to develop a thermo-mechanical strategy to create a radial elasticity gradient in a β metastable Ti-Nb-Zr alloy, and to characterize it in terms of microstructural and mechanical properties. A first investigation was conducted on thin samples of Ti-20Nb-6Zr (at.%) submitted to various thermo-mechanical treatments. Microstructure-properties relationships and elastic variability of this alloy were determined performing uniaxial tensile tests, X-ray diffraction and scanning and transmission electron microscopies. Based on these preliminary results, mechanical deformation was identified as a potential way to lower the elastic modulus of the alloy. In order to create elastically graded pieces, shot-peening was therefore carried out on thicker samples to engender surface deformation. In this second part of the work, local mechanical properties were evaluated by instrumented micro-indentation. Experimental observations demonstrated that shot-peening enabled to locally induce martensitic transformation on surface, and a decrease in indentation elastic modulus from 85 to 65 GPa over 400 μm was highlighted. Surface deformation proved to be an efficient way of creating an elasticity gradient in β metastable titanium alloys. This combination of material and process could be suitable to produce dental implants with mechanically enhanced biocompatibility.
Effect of Y2O3 Addition on High-Temperature Oxidation of Binderless Tungsten Carbide
Authors: Wang Jinfang , Zuo Dunwen , Zhu Liu , Tu Zhibiao , Lin Xiao , Wu Yinan , Li Weiwei , Zhang Xiaoqiong
Published: March 2021

High-temperature oxidation tests were carried out on binderless tungsten carbide (WC) with different Y2O3 contents (0, 1, 2, 3, and 4 wt.%) and on YG3 cemented carbide. Results demonstrated that the addition of Y2O3 led to a significant improvement in the high-temperature oxidation resistance of binderless tungsten carbide compared with those of YG3 cemented carbide and pure tungsten carbide. After oxidation at 800°C for 120 min, the oxidation weight gain of binderless tungsten carbide with 1 wt.% Y2O3 was 58.54 mg cm−2, corresponding to the reduction by 47.7% compared with YG3 cemented carbide. In the high temperature oxidation process, WC in the triangle grain boundary was first oxidized to Y2WO6 due to the high activity of Y2O3 which is present mainly in the WC grain boundaries. The transport of W4+ outward along the grain boundary and the diffusion of O2− inward along the grain boundary were hindered by Y2WO6 with the high ionic radius and thus the antioxidant capacity of binderless tungsten carbide was improved. Meanwhile, the adhesive ability of oxidation layer on the substrate was enhanced with the “pinning effect” of Y2WO6, which also led to the improvement of oxidation resistance. With the Y2O3 content increasing from 1 to 4 wt.%, the antioxidant properties of binderless tungsten carbide gradually declined, and the antioxidant performance of binderless tungsten carbide with 1 wt.% Y2O3 was found to be the best.
Experience With the Use of the MicroDTTect Device for the Diagnosis of Low-Grade Chronic Prosthetic Joint Infections in a Routine Setting
Authors: Kolenda Camille , Josse Jérôme , Batailler Cécile , Faure Allison , Monteix Alice , Lustig Sébastien , Ferry Tristan , Laurent Frédéric , Dupieux Céline
Published: March 2021

Background: In prosthetic joint infections (PJIs), identification of the causative microorganisms is critical to successfully adapt and optimize treatment. However, microbiological diagnosis of PJIs remains a challenge notably because bacteria are embedded in biofilm adhered to the prosthetic material. Recently, dithiothreitol (DTT) treatment of prosthesis has been proposed as a new strategy to release bacteria from biofilm and to improve the yield of microbiological diagnosis. In this study, we evaluated the interest of a commercial device using DTT, the MicroDTTect system (Heraeus, Hanau, Germany), for the diagnosis of low-grade chronic PJIs, compared to the conventional culture of periprosthetic tissue (PPT) samples.

Methods: Twenty patients undergoing a surgery procedure for removal of prosthetic material because of a suspicion of low-grade PJI without pre-operative microbiological documentation were included (NCT04371068). Bacteriological results using the fluid obtained after prosthesis treatment with the MicroDTTect system were compared to results obtained with conventional culture of PPT samples.

Results: All the bacteria considered as responsible for PJIs recovered from culture of PPT samples were also detected using the MicroDTTect device. For one patient, an additional bacterial isolate (Staphylococcus haemolyticus) suspected to be involved in a polymicrobial PJI was identified using DTT treatment. Time to positivity of the cultures was also reduced using the MicroDTTect system, notably in case of Cutibacterium acnes infection. However, probable bacterial contaminants were found (MicroDTTect system, n = 5; PPT samples, n = 1).

Conclusion: This study showed that DTT treatment of the prosthetic component using the MicroDTTect device could improve the microbiological diagnosis of low-grade PJIs.
Resequencing of Microbial Isolates: A Lab Module to Introduce Novices to Command-Line Bioinformatics
Authors: Petrie Katherine Lynn , Xie Rujia
Published: March 2021

Familiarity with genome-scale data and the bioinformatic skills to analyze it have become essential for understanding and advancing modern biology and human health, yet many undergraduate biology majors are never exposed to hands-on bioinformatics. This paper presents a module that introduces students to applied bioinformatic analysis within the context of a research-based microbiology lab course. One of the most commonly used genomic analyses in biology is resequencing: determining the sequence of DNA bases in a derived strain of some organism, and comparing it to the known ancestral genome of that organism to better understand the phenotypic differences between them. Many existing CUREs — Course Based Undergraduate Research Experiences — evolve or select new strains of bacteria and compare them phenotypically to ancestral strains. This paper covers standardized strategies and procedures, accessible to undergraduates, for preparing and analyzing microbial whole-genome resequencing data to examine the genotypic differences between such strains. Wet-lab protocols and computational tutorials are provided, along with additional guidelines for educators, providing instructors without a next-generation sequencing or bioinformatics background the necessary information to incorporate whole-genome sequencing and command-line analysis into their class. This module introduces novice students to running software at the command-line, giving them exposure and familiarity with the types of tools that make up the vast majority of open-source scientific software used in contemporary biology. Completion of the module improves student attitudes toward computing, which may make them more likely to pursue further bioinformatics study.
Impact of Synonymous Genome Recoding on the HIV Life Cycle
Authors: Jordan-Paiz Ana , Franco Sandra , Martínez Miguel Angel
Published: March 2021

Synonymous mutations within protein coding regions introduce changes in DNA or messenger (m) RNA, without mutating the encoded proteins. Synonymous recoding of virus genomes has facilitated the identification of previously unknown virus biological features. Moreover, large-scale synonymous recoding of the genome of human immunodeficiency virus type 1 (HIV-1) has elucidated new antiviral mechanisms within the innate immune response, and has improved our knowledge of new functional virus genome structures, the relevance of codon usage for the temporal regulation of viral gene expression, and HIV-1 mutational robustness and adaptability. Continuous improvements in our understanding of the impacts of synonymous substitutions on virus phenotype – coupled with the decreased cost of chemically synthesizing DNA and improved methods for assembling DNA fragments – have enhanced our ability to identify potential HIV-1 and host factors and other aspects involved in the infection process. In this review, we address how silent mutagenesis impacts HIV-1 phenotype and replication capacity. We also discuss the general potential of synonymous recoding of the HIV-1 genome to elucidate unknown aspects of the virus life cycle, and to identify new therapeutic targets.
Predictors of New-Onset Epilepsy in People With Younger-Onset Neurocognitive Disorders
Authors: Wang Xinshi , Loi Samantha M. , Foster Emma , Chen Zhibin , Velakoulis Dennis , Kwan Patrick
Published: March 2021

Objective: People with neurocognitive disorders (NCDs) have an increased risk of epilepsy. However, most studies investigating the risk of seizures in people with NCDs are limited to those with Alzheimer's disease (AD) and vascular dementia (VD), and those who developed dementia after age 65 years. A knowledge gap exists regarding factors associated with development of epilepsy in people with younger-onset NCD, and those with non-AD and non-VD dementia subtypes. In this study, we aimed to identify the factors associated with the development of epilepsy in people with younger-onset NCDs of varied etiologies, the majority of whom had symptom onset prior to age 65 years.

Participants and Methods: This was a retrospective study reviewing the medical records of consecutive people admitted with cognitive impairment to a tertiary neuropsychiatry unit between 1 January 2004 and 30 April 2019. People diagnosed with primary NCDs were included in the analysis. The prevalence and characteristics of epilepsy were described. The factors associated with developing epilepsy were identified in a binary logistic regression model.

Results: A total of 427 people were included. One hundred fourteen had Alzheimer's disease, 104 frontotemporal dementia, 51 vascular dementia, 69 movement disorder-associated dementia, and 89 unspecified NCD. The median age on admission was 59 years (range 33–86) and 75.2% (n = 321/427) had young-onset NCD with onset before 65 years of age. 40/427 (9.4%) people had epilepsy, and epilepsy onset clustered between 2 years before and 6 years after the onset of cognitive decline in 80% (n = 32/40). The most frequent seizure type was focal to bilateral tonic-clonic seizure (35%, n = 14/40). Most of the people (94.7%, n = 36/38) achieved seizure freedom with one or two antiseizure medications. People with unspecified NCD (compared to frontotemporal dementia and movement disorder-associated dementia, age of onset of NCDs ≤50 years, and current smoking status were independently associated with higher risk of developing epilepsy.

Conclusion: Epilepsy is common in people with younger-onset NCDs, and a high index of suspicion is warranted particularly for those with unspecified subtype and smoking status. Smoking reduction or cessation should be further investigated as a potentially modifiable factor for risk reduction.
Ankfy1 Is Involved in the Maintenance of Cerebellar Purkinje Cells
Authors: Chang Liansheng , Soomro Shahid Hussain , Zhang Hongfeng , Fu Hui
Published: March 2021

Purkinje cells are critical for the function of cerebellum. The degeneration of Purkinje cells leads to defects in motion control. We have found that Purkinje cells specifically express Ankfy1 protein during development and in adult. This protein seems to play minor functions during development as Ankfy1 knockout mice appear normal till adult. However, at 9-month-old, knockout mice showed abnormal cerebellum with reduced vermis size and developed defective motor function. Further investigation demonstrated that the cerebellum of the mutant mouse has lost most of its Purkinje cells, while other cerebellar cells remained largely normal. Our data suggested that theAnkfy1might be important for the maintenance of cerebellar Purkinje cells.
C21orf91 Regulates Oligodendroglial Precursor Cell Fate—A Switch in the Glial Lineage?
Authors: Reiche Laura , Göttle Peter , Lane Lydie , Duek Paula , Park Mina , Azim Kasum , Schütte Jana , Manousi Anastasia , Schira-Heinen Jessica , Küry Patrick
Published: March 2021

Neuropathological diseases of the central nervous system (CNS) are frequently associated with impaired differentiation of the oligodendroglial cell lineage and subsequent alterations in white matter structure and dynamics. Down syndrome (DS), or trisomy 21, is the most common genetic cause for cognitive impairments and intellectual disability (ID) and is associated with a reduction in the number of neurons and oligodendrocytes, as well as with hypomyelination and astrogliosis. Recent studies mainly focused on neuronal development in DS and underestimated the role of glial cells as pathogenic players. This also relates to C21ORF91, a protein considered a key modulator of aberrant CNS development in DS. We investigated the role of C21orf91 ortholog in terms of oligodendrogenesis and myelination using database information as well as through cultured primary oligodendroglial precursor cells (OPCs). Upon modulation of C21orf91 gene expression, we found this factor to be important for accurate oligodendroglial differentiation, influencing their capacity to mature and to myelinate axons. Interestingly, C21orf91 overexpression initiates a cell population coexpressing astroglial- and oligodendroglial markers indicating that elevated C21orf91 expression levels induce a gliogenic shift towards the astrocytic lineage reflecting non-equilibrated glial cell populations in DS brains.
Glial Cells in Glaucoma: Friends, Foes, and Potential Therapeutic Targets
Authors: García-Bermúdez Mariana Y. , Freude Kristine K. , Mouhammad Zaynab A. , van Wijngaarden Peter , Martin Keith K. , Kolko Miriam
Published: March 2021

Glaucoma is the second leading cause of blindness worldwide, affecting ~80 million people by 2020 (1,2). The condition is characterized by a progressive loss of retinal ganglion cells (RGCs) and their axons accompanied by visual field loss. The underlying pathophysiology of glaucoma remains elusive. Glaucoma is recognized as a multifactorial disease, and lowering intraocular pressure (IOP) is the only treatment that has been shown to slow the progression of the condition. However, a significant number of glaucoma patients continue to go blind despite intraocular pressure-lowering treatment (2). Thus, the need for alternative treatment strategies is indisputable. Accumulating evidence suggests that glial cells play a significant role in supporting RGC function and that glial dysfunction may contribute to optic nerve disease. Here, we review recent advances in understanding the role of glial cells in the pathophysiology of glaucoma. A particular focus is on the dynamic and essential interactions between glial cells and RGCs and potential therapeutic approaches to glaucoma by targeting glial cells.
Association of Diabetic Retinopathy With Stroke: A Systematic Review and Meta-Analysis
Authors: Hu Kaiyan , Jiang Mengyao , Zhou Qi , Zeng Weiting , Lan Xuhong , Gao Qianqian , Mei Fan , Zhao Li , Chen Fei , Wu Anhu , Tao Gongcai , Mou Chenghua , Ma Bin
Published: March 2021

Background: The population-based studies conducted thus far do not provide conclusive evidence of the link between diabetic retinopathy (DR) and stroke. The aim of the present systematic review was to determine whether DR is specifically associated with stroke.

Methods: MEDLINE, Embase, and Web of Science were systematically searched from their inception to July 31, 2020. All cohort studies that reported associations between the presence of DR and incident stroke were included. The pooled hazard ratios (HRs), pooled risk ratios (RRs), and 95% confidence intervals (CIs) were calculated.

Results: The meta-analysis included 19 cohort studies involving 81,452 diabetic patients. The pooled effect size of any DR related to stroke was 1.25 for HR (95% CI: 1.12–1.39; P < 0.0001) and 1.96 for RR (95% CI: 1.60–2.39; P < 0.0001). Subgroup analysis for the type of diabetes yielded pooled HR of 1.29 (95% CI: 1.10–1.50; P = 0.001) in patients with type 2 diabetes mellitus (T2DM). The pooled RR was 2.29 (95% CI: 1.77–2.96; P < 0.0001) in patients with T2DM. Two studies addressed the DR-related stroke among type 1 diabetes mellitus (T1DM) patients. One study found a significant association between DR and stroke (OR: 1.6; 95% CI: 1.1–2.3; P < 0.01), while the other did not identify an association between these two conditions (RR: 1.40; 95% CI: 0.62–2.18; P = 0.178).

Conclusions: The presence of DR is associated with an increased risk of stroke in diabetic patients. This correlation is robust in T2DM patients but uncertain in T1DM patients. Our findings indicate that DR is an important biomarker for the prediction of stroke. To further validate the role of DR in stroke-risk stratification, additional research is required on the association between the stage of DR and stroke risk, and more studies including T1DM patients are necessary.
Magnetization Transfer Ratio in Lower Limbs of Late Onset Pompe Patients Correlates With Intramuscular Fat Fraction and Muscle Function Tests
Authors: Nuñez-Peralta Claudia , Montesinos Paula , Alonso-Jiménez Alicia , Alonso-Pérez Jorge , Reyes-Leiva David , Sánchez-González Javier , Llauger-Roselló Jaume , Segovia Sonia , Belmonte Izaskun , Pedrosa Irene , Martínez-Noguera Antonio , Matellini-Mosca Briano , Walter Glenn , Díaz-Manera Jordi
Published: March 2021

Objectives: Magnetization transfer (MT) imaging exploits the interaction between bulk water protons and protons contained in macromolecules to induce signal changes through a special radiofrequency pulse. MT detects muscle damage in patients with neuromuscular conditions, such as limb-girdle muscular dystrophies or Charcot-Marie-Tooth disease, which are characterized by progressive fiber loss and replacement by fatty tissue. In Pompe disease, in which there is, in addition, an accumulation of glycogen inside the muscle fibers, MT has not been tested yet. Our aim is to estimate MT ratio (MTR) in the skeletal muscle of these patients and correlate it with intramuscular fat fraction (FF) and results of muscle function tests.

Methods: We obtained two-point axial Dixon and Dixon-MT sequences of the right thigh on a 1.5 Teslas MRI scanner in 60 individuals, including 29 late onset Pompe disease patients, 2 patients with McArdle disease, and 29 age and sex matched healthy controls. FF and MTR were estimated. Muscle function using several muscle function tests, including quantification of muscle strength, timed test quality of life scales, conventional spirometry obtaining forced vital capacity while sitting and in the supine position, were assessed in all patients.

Results: MTR was significantly lower in Pompe patients compared with controls (45.5 ± 8.5 vs. 51.7 ± 2.3, Student T-test, p < 0.05). There was a negative correlation between the MTR and FF muscles studied (correlation coefficient: −0.65, Spearman test: p < 0.05). MTR correlated with most of the muscle function test results. We analyzed if there was any difference in MTR values between Pompe patients and healthy controls in those muscles that did not have an increase in fat, a measure that could be related to the presence of glycogen in skeletal muscles, but we did not identify significant differences except in the adductor magnus muscle (48.4 ± 3.6 in Pompe vs. 51 ± 1.3 in healthy controls, Student T-test = 0.023).

Conclusions: MTR is a sensitive tool to identify muscle loss in patients with Pompe disease and shows a good correlation with muscle function tests. Therefore, the MT technique can be useful in monitoring muscle degeneration in Pompe disease in clinical trials or natural history studies.
Construction of Gene Modules and Analysis of Prognostic Biomarkers for Cervical Cancer by Weighted Gene Co-Expression Network Analysis
Authors: Liu Jiamei , Liu Shengye , Yang Xianghong
Published: March 2021

Background

Despite advances in the understanding of neoplasm, patients with cervical cancer still have a poor prognosis. Identifying prognostic markers of cervical cancer may enable early detection of recurrence and more effective treatment.

Methods

Gene expression profiling data were acquired from the Gene Expression Omnibus database. After data normalization, genes with large variation were screened out. Next, we built co-expression modules by using weighted gene co-expression network analysis to investigate the relationship between the modules and clinical traits related to cervical cancer progression. Functional enrichment analysis was also applied on these co-expressed genes. We integrated the genes into a human protein-protein interaction (PPI) network to expand seed genes and build a co-expression network. For further analysis of the dataset, the Cancer Genome Atlas (TCGA) database was used to identify seed genes and their correlation to cervical cancer prognosis. Verification was further conducted by qPCR and the Human Protein Atlas (HPA) database to measure the expression of hub genes.

Results

Using WGCNA, we identified 25 co-expression modules from 10,016 genes in 128 human cervical cancer samples. After functional enrichment analysis, the magenta, brown, and darkred modules were selected as the three most correlated modules for cancer progression. Additionally, seed genes in the three modules were combined with a PPI network to identify 31 tumor-specific genes. Hierarchical clustering and Gepia results indicated that the expression quantity of hub genes NDC80, TIPIN, MCM3, MCM6, POLA1, and PRC1 may determine the prognosis of cervical cancer. Finally, TIPIN and POLA1 were further filtered by a LASSO model. In addition, their expression was identified by immunohistochemistry in HPA database as well as a biological experiment.

Conclusion

Our research provides a co-expression network of gene modules and identifies TIPIN and POLA1 as stable potential prognostic biomarkers for cervical cancer.
COL5A2 Promotes Proliferation and Invasion in Prostate Cancer and Is One of Seven Gleason-Related Genes That Predict Recurrence-Free Survival
Authors: Ren Xiaohan , Chen Xinglin , Fang Kai , Zhang Xu , Wei Xiyi , Zhang Tongtong , Li Guangyao , Lu Zhongwen , Song Ninghong , Wang Shangqian , Qin Chao
Published: March 2021

Extensive research has revealed that the score derived from the Gleason grading system plays a pivotal role in predicting prostate cancer (PCa) progression. However, the underlying involvement of Gleason-related genes in PCa requires further investigation. This study aimed to identify Gleason-related genes with the potential to guide PCa therapy and future research. Differentially expressed genes (DEGs) were identified by comparing PCa tissues with high or low Gleason scores using the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) databases. R v3.6.1, SPSS v23, and ImageJ software were used for all analyses. An effective recurrence-free survival (RFS) predictive model based on seven Gleason-related genes was established and validated (TCGA, AUC = 0.803; five years, AUC = 0.740; three years, AUC = 0.722; one year, AUC = 0.711; GSE46602, AUC = 0.766; five years, AUC = 0.808; three years, AUC = 0.723; one year, AUC = 0.656; GSE116918, AUC = 0.788; five years, AUC = 0.704; three years, AUC = 0.693; one year, AUC = 0.996). Calibration and nomogram plots were conducted. Weighted correlation network analysis (WGCNA) was used, and COL5A2 was selected for further analysis. The results from in vitro experiments demonstrated that COL5A2 was upregulated in PCa with high Gleason scores. The knockdown of COL5A2 inhibited cell proliferation and invasion in PC-3 and LNCaP cell lines. Meanwhile, COL5A2 displayed a strong association with immune infiltration, which might be an underlying immunotherapy target for PCa. We successfully established a robust RFS predictive model. The findings from this study indicated that COL5A2 could promote cell proliferation and invasion in PCa.
Serum Protein N-Glycosylation Signatures of Neuroblastoma
Authors: Qin Wenjun , Pei Hao , Li Xiaobing , Li Jia , Yao Xuelian , Zhang Rufang
Published: March 2021

Background

Neuroblastoma is the most common extracranial childhood solid tumor which accounts for 10% of the malignancies and 15% of the cancer fatalities in children. N-glycosylation is one of the most frequent post-translation protein modification playing a vital role in numerous cancers. N-glycosylation changes in neuroblastoma patient serum have not been studied in existing reports. The comprehensive analyses of serum N-glycomics in neuroblastoma can provide useful information of potential disease biomarkers and new insights of the pathophysiology in neuroblastoma.

Methods

The total serum protein N-glycosylation was analyzed in 33 neuroblastoma patients and 40 age- and sex-matched non-malignant controls. N-glycans were enzymatically released, derivatized to discriminate linkage-specific sialic acid, purified by HILIC-SPE, and identified by MALDI-TOF-MS. Peak areas were acquired by the software of MALDI-MS sample acquisition, processed and analyzed by the software of Progenesis MALDI.

Results

Three glyco-subclasses and six individual N-glycans were significantly changed in neuroblastoma patients compared with controls. The decreased levels of high mannose N-glycans, hybrid N-glycans, and increased levels of α2,3-sialylated N-glycans, multi-branched sialylated N-glycans were observed in neuroblastoma patients. what is more, a glycan panel combining those six individual N-glycans showed a strong discrimination performance, with an AUC value of 0.8477.

Conclusions

This study provides new insights into N-glycosylation characteristics in neuroblastoma patient serum. The analyses of total serum protein N-glycosylation could discriminate neuroblastoma patients from non-malignant controls. The alterations of the N-glycomics may play a suggestive role for neuroblastoma diagnosis and advance our understanding of the pathophysiology in neuroblastoma.
Integrative Analysis of the Expression of SIGLEC Family Members in Lung Adenocarcinoma via Data Mining
Authors: Zhang Haiyan , Xie Yongfei , Hu Zhi , Yu Hong , Xie Xiang , Ye Yingchun , Xu Wenfeng , Nian Siji , Yuan Qing
Published: March 2021

Background: Sialic acid-binding immunoglobulin-type lectin (SIGLEC) family members are involved in regulating immune-cell activation, proliferation, and apoptosis, and they play an important role in tumor development. However, their expression and correlation with immune molecules in lung adenocarcinoma (LUAD) remain unclear.

Methods: We utilized Gene Expression Profiling Interactive Analysis, Kaplan–Meier analysis, the limma package in R/Bioconductor, the University of California Santa Cruz Cancer Genome Browser, cBioPortal, STRING, Cytoscape, DAVID, and the Tumor Immune Estimation Resource for gene and protein profiling and analyses.

Results: The results showed that SIGLEC10 and SIGLEC15 levels were upregulated in LUAD, whereas SIGLEC1, CD22 (SIGLEC2), CD33, myelin-associated glycoprotein (SIGLEC4), SIGLEC5, SIGLEC6, SIGLEC7, SIGLEC8, SIGLEC11, and SIGLEC14 levels were significantly downregulated, with their low expression associated with poor overall survival. Moreover, we observed high SIGLEC-mutation rates (22%) in LUAD patients, with SIGLEC functions determined as primarily involved in regulating the immune response, signal transduction, inflammatory response, and cell adhesion. Furthermore, we found that SIGLEC expression was significantly correlated with immune-cell infiltration, especially macrophages, neutrophils, and dendritic cells, and highly associated with immune molecules such as CD80, CD86, CD28, B-cell-activating factor, programmed cell death 1 ligand 2, and colony stimulating factor 1 receptor.

Conclusion: These results provide insight into the potential molecular mechanism associated with SIGLEC-related development of LUAD, as well as clues for screening biomarkers and therapeutic targets.
Identification of a Six Gene Prognosis Signature for Papillary Thyroid Cancer Using Multi-Omics Methods and Bioinformatics Analysis
Authors: Ren He , Liu Xin , Li Fuxin , He Xianghui , Zhao Na
Published: March 2021

Papillary thyroid carcinoma (PTC) is the most common subtype of thyroid cancer. PTC is typically curable with an excellent survival rate; however, some patients experience disease recurrence or death. This study aimed to discover potential key genes and signaling pathways of PTC, which could provide new insights for thyroid lesions. Four GEO microarray datasets were integrated to screen for candidate genes involved in PTC progression. A total of 164 upregulated and 168 downregulated differentially expressed genes (DEGs) were screened. Gene Ontology/Kyoto Encyclopedia of Genes and Genomes were used in pathway enrichment analyses for DEGs. A protein-protein interaction network was then built and analyzed utilizing STRING and Cytoscape, followed by the identification of 13 hub genes by cytoHubba. CDH3, CTGF, CYR61, OGN, FGF13, and CHRDL1 were selected through survival analyses. Furthermore, immune infiltration, mutations and methylation analysis indicated that these six hub genes played vital roles in immune surveillance and tumor progression. ROC and K-M plots showed that these genes had good prognostic values for PTC which was validated by TCGA dataset. Finally, GSEA for a single hub gene revealed that each candidate hub gene had close associations with PTC development. These findings provided new insights into PTC pathogenesis and identified six candidate gene prognosis signature for PTC.
miR-186 Inhibits Liver Cancer Stem Cells Expansion via Targeting PTPN11
Authors: Yao Haochen , Yang Ziting , Lou Yan , Huang Juanjuan , Yang Pinghua , Jiang Weiqi , Chen Shuai
Published: March 2021

MicroRNAs (miRNAs) participated in the regulation of tumorigenesis, progression, metastasis, recurrence and chemo-resistance of cancers. However, the potential function of miRNAs in cancer stem cells (CSCs) or tumor-initiating cells (T-ICs) was not clearly elucidated. In the present study, we found that miR-186 expression was reduced in liver CSCs. Functional studies showed that miR-186 knockdown facilitated liver CSCs self-renewal and tumorigenesis. Conversely, forced miR-186 expression suppressed liver CSCs self-renewal and tumorigenesis. Mechanically, miR-186 downregulated PTPN11 via binding to its 3’-UTR in liver CSCs. The correlation of miR-186 and PTPN11 was confirmed in Hepatocellular carcinoma (HCC) patients’ tissues. Further study showed that interference of PTPN11 can abolished the discrepancy between miR-186 mimic and control HCC cells in self-renewal and the proportion of CSCs. Additionally, we found that miR-186 overexpression HCC cells were more sensitive to cisplatin treatment. Clinical cohort analysis showed that HCC patients with high miR-186 were benefited more from transcatheter arterial chemoembolization (TACE) treatment. In conclusion, our study demonstrates a new regulation mechanism of liver CSCs, a new target for HCC, and a biomarker for postoperative TACE.
Dosing Strategies for Improving the Risk-Benefit Profile of Ponatinib in Patients With Chronic Myeloid Leukemia in Chronic Phase
Authors: Castagnetti Fausto , Pane Fabrizio , Rosti Gianantonio , Saglio Giuseppe , Breccia Massimo
Published: March 2021

The treatment of chronic myeloid leukemia (CML) has been advanced by the development of small-molecule tyrosine kinase inhibitors (TKIs), which target the fusion protein BCR-ABL1 expressed by the Philadelphia chromosome. Ponatinib is a 3rd generation TKI that binds BCR-ABL1 with high affinity and inhibits most BCR-ABL1 mutants, including the T315I mutation. The approved starting dose of ponatinib is 45 mg once daily (full dose), however, the need for a full dose, especially in patients with dose adjustments due to tolerability problems, remains undemonstrated. Lower starting doses of ponatinib (30 mg or 15 mg once daily) for patients “with lesser degrees of resistance or multiple intolerances, especially those with an increased cardiovascular risk profile” has been recommended by the 2020 European LeukemiaNet. However, the available literature and guidance on the use of ponatinib at low dosage are limited. The objective of this paper is to describe how we select ponatinib dosage for CML patients in chronic phase in our clinical practice based on the available evidence and our clinical experience. We propose dosing regimens for the optimal starting dose for six generic cases of CML patients in chronic phase eligible for the switch to ponatinib and provide an algorithm to guide ponatinib dosing during treatment.
Clinical Application of Liquid Biopsy in Non-Hodgkin Lymphoma
Authors: Lv Liwei , Liu Yuanbo
Published: March 2021

Non-Hodgkin lymphoma (NHL) is a common type of hematological malignant tumor, composed of multiple subtypes that originate from B lymphocytes, T lymphocytes, and natural killer cells. A diagnosis of NHL depends on the results of a pathology examination, which requires an invasive tissue biopsy. However, due to their invasive nature, tissue biopsies have many limitations in clinical applications, especially in terms of evaluating the therapeutic response and monitoring tumor progression. To overcome these limitations of traditional tissue biopsies, a technique known as “liquid biopsies” (LBs) was proposed. LBs refer to noninvasive examinations that can provide biological tumor data for analysis. Many studies have shown that LBs can be broadly applied to the diagnosis, treatment, prognosis, and monitoring of NHL. This article will briefly review various LB methods that aim to improve NHL management, including the evaluation of cell-free DNA/circulating tumor DNA, microRNA, and tumor-derived exosomes extracted from peripheral blood in NHL.
Laboratory Markers in the Management of Pediatric Polytrauma: Current Role and Areas of Future Research
Authors: Weber Birte , Lackner Ina , Braun Christian Karl , Kalbitz Miriam , Huber-Lang Markus , Pressmar Jochen
Published: March 2021

Severe trauma is the most common cause of mortality in children and is associated with a high socioeconomic burden. The most frequently injured organs in children are the head and thorax, followed by the extremities and by abdominal injuries. The efficient and early assessment and management of these injuries is essential to improve patients' outcome. Physical examination as well as imaging techniques like ultrasound, X-ray and computer tomography are crucial for a valid early diagnosis. Furthermore, laboratory analyses constitute additional helpful tools for the detection and monitoring of pediatric injuries. Specific inflammatory markers correlate with post-traumatic complications, including the development of multiple organ failure. Other laboratory parameters, including lactate concentration, coagulation parameters and markers of organ injury, represent further clinical tools to identify trauma-induced disorders. In this review, we outline and evaluate specific biomarkers for inflammation, acid-base balance, blood coagulation and organ damage following pediatric polytrauma. The early use of relevant laboratory markers may assist decision making on imaging tools, thus contributing to minimize radiation-induced long-term consequences, while improving the outcome of children with multiple trauma.
The Parameters of the Field Emission Model and the Fabrication of Zinc Oxide Nanorod Arrays/Graphene Film
Authors: Yang JianJun , Shao ShuangShuang , Li YaXin , Wang YueHui , Feng Chi
Published: March 2021

A large-scale growth of zinc oxide (ZnO) nanorod arrays on graphene sheets was fabricated by a hydrothermal technique, and the Fowler–Nordheim theory was used to build a model to describe the properties of the arrays’ field emission. The results indicated that the morphological characteristics of the ZnO nanorods grown on the graphene sheets can be easily tuned by varying the reaction time and concentrations of the reaction solution. The regular ordered ZnO nanorods arrays on the graphene sheets were obtained under the appropriate experimental conditions. Further, this composite cathode was demonstrated to possess excellent field emission properties due to the outstanding mechanical and electrical properties of graphene. The field emission current density of the composite cathode reached 1,448 μA cm–2 at the electric field of 16.5 V μm–1. The key parameter, field enhancement factor, reached 6,366, while the pure graphene cathode field is about 1,660. These specific nanorod arrays with enhancement of the field emission properties would be useful to sensor or modulator units for accessing networks.
Construction of Prognostic Risk Prediction Model of Oral Squamous Cell Carcinoma Based on Nine Survival-Associated Metabolic Genes
Authors: Huang Zhen-Dong , Yao Yang-Yang , Chen Ting-Yu , Zhao Yi-Fan , Zhang Chao , Niu Yu-Ming
Published: March 2021

The aim was to investigate the independent prognostic factors and construct a prognostic risk prediction model to facilitate the formulation of oral squamous cell carcinoma (OSCC) clinical treatment plan. We constructed a prognostic model using univariate COX, Lasso, and multivariate COX regression analysis and conducted statistical analysis. In this study, 195 randomly obtained sample sets were defined as training set, while 390 samples constituted validation set for testing. A prognostic model was constructed using regression analysis based on nine survival-associated metabolic genes, among which PIP5K1B, NAGK, and HADHB significantly down-regulated, while MINPP1, PYGL, AGPAT4, ENTPD1, CA12, and CA9 significantly up-regulated. Statistical analysis used to evaluate the prognostic model showed a significant different between the high and low risk groups and a poor prognosis in the high risk group (P < 0.05) based on the training set. To further clarify, validation sets showed a significant difference between the high-risk group with a worse prognosis and the low-risk group (P < 0.05). Independent prognostic analysis based on the training set and validation set indicated that the risk score was superior as an independent prognostic factor compared to other clinical characteristics. We conducted Gene Set Enrichment Analysis (GSEA) among high-risk and low-risk patients to identify metabolism-related biological pathways. Finally, nomogram incorporating some clinical characteristics and risk score was constructed to predict 1-, 2-, and 3-year survival rates (C-index = 0.7). The proposed nine metabolic gene prognostic model may contribute to a more accurate and individualized prediction for the prognosis of newly diagnosed OSCC patients, and provide advice for clinical treatment and follow-up observations.
Overexpression of SlGATA17 Promotes Drought Tolerance in Transgenic Tomato Plants by Enhancing Activation of the Phenylpropanoid Biosynthetic Pathway
Authors: Zhao Tingting , Wu Tairu , Pei Tong , Wang Ziyu , Yang Huanhuan , Jiang Jingbin , Zhang He , Chen Xiuling , Li Jingfu , Xu Xiangyang
Published: March 2021

GATA transcription factors (TFs) are widely distributed in eukaryotes. Some GATA TFs have been shown to be related to photosynthesis, germination, circadian rhythm, and other functions in plants. Our previous study found that some members of this family have obvious responses when tomato plants are subjected to drought stress, in which the SlGATA17 gene is significantly upregulated. To further verify the function of this gene under drought stress, we constructed tomato lines with this gene overexpressed. Phenotypic and physiological indicators indicated that the SlGATA17-overexpressing plants were more drought tolerant than the wild-type plants. Transcriptomic sequencing results showed that the overexpression of the SlGATA17 gene improved the activity of the phenylpropanoid biosynthesis pathway. The PAL enzyme activity assay results confirmed that the initial activity of this pathway was enhanced in transgenic plants, especially in the initial response stage, indicating that the SlGATA17 gene regulates the drought resistance of tomato plants by regulating the activity of the phenylpropanoid biosynthesis pathway.
Psychological Impact of the Lockdown in Italy Due to the COVID-19 Outbreak: Are There Gender Differences?
Authors: Rania Nadia , Coppola Ilaria
Published: March 2021

The COVID-19 emergency has hit the whole world, finding all countries unprepared to face it. The first studies focused on the medical aspects, neglecting the psychological dimension of the populations that were forced to face changes in everyday life and in some cases to stay forcedly at home in order to reduce contagion. The present research was carried out in Italy, one of the countries hardest hit by the pandemic. The aim was to analyze the perception of happiness, mental health, and the sense of loneliness experienced by adults during the lockdown due to the COVID pandemic. Specifically, the variables will be examined in relation to gender difference, living alone, with partner, or with partner and children. The research followed a quantitative approach using an online questionnaire. The project involved 1100 subjects from whom 721 participants (75.5% women) were extrapolated. Of them, 17.3% claimed to live alone, 39.5% with their partner, and 43.1% with their partner and children. The results show that people in general experienced a lower level of happiness and mental health and higher levels of loneliness compared to normative sample. The lockdown and pandemic condition due to COVID-19 seems to have canceled the gender differences in the perception of happiness and mental health, while it seems to have increased the perception of loneliness experienced by males compared to the pre-pandemic condition. In addition, those who lived alone perceived a greater level of loneliness than those who lived with their partner or partner and children. Unexpectedly, no significant differences emerged regarding the level of happiness and mental health between those who had direct contact with the virus and those who did not. These data should make political decision-makers reflect on the need to pay more attention to the implications that such drastic measures as a lockdown can have on people’s psychological well-being.