bluuebunny/crossref_metadata_2025 huggingface dataset:
Fracture risk assessment in diabetes mellitus
Authors: Chen Weiwei , Mao Min , Fang Jin , Xie Yikai , Rui Yongjun
Published: September 2022

Growing evidence suggests that diabetes mellitus is associated with an increased risk of fracture. Bone intrinsic factors (such as accumulation of glycation end products, low bone turnover, and bone microstructural changes) and extrinsic factors (such as hypoglycemia caused by treatment, diabetes peripheral neuropathy, muscle weakness, visual impairment, and some hypoglycemic agents affecting bone metabolism) probably contribute to damage of bone strength and the increased risk of fragility fracture. Traditionally, bone mineral density (BMD) measured by dual x-ray absorptiometry (DXA) is considered to be the gold standard for assessing osteoporosis. However, it cannot fully capture the changes in bone strength and often underestimates the risk of fracture in diabetes. The fracture risk assessment tool is easy to operate, giving it a certain edge in assessing fracture risk in diabetes. However, some parameters need to be regulated or replaced to improve the sensitivity of the tool. Trabecular bone score, a noninvasive tool, indirectly evaluates bone microstructure by analyzing the texture sparsity of trabecular bone, which is based on the pixel gray level of DXA. Trabecular bone score combined with BMD can effectively improve the prediction ability of fracture risk. Quantitative computed tomography is another noninvasive examination of bone microstructure. High-resolution peripheral quantitative computed tomography can measure volume bone mineral density. Quantitative computed tomography combined with microstructure finite element analysis can evaluate the mechanical properties of bones. Considering the invasive nature, the use of microindentation and histomorphometry is limited in clinical settings. Some studies found that the changes in bone turnover markers in diabetes might be associated with fracture risk, but further studies are needed to confirm this. This review focused on summarizing the current development of these assessment tools in diabetes so as to provide references for clinical practice. Moreover, these tools can reduce the occurrence of fragility fractures in diabetes through early detection and intervention.
Which is the optimal antiobesity agent for patients with nonalcoholic fatty liver disease?
Authors: Tsankof Alexandra , Neokosmidis Georgios , Koureta Evgenia , Veneti Stavroula , Cholongitas Evangelos , Tziomalos Konstantinos
Published: September 2022

Nonalcoholic fatty liver disease (NAFLD) is the commonest chronic liver disease and affects a considerable proportion of the general population worldwide. Obesity is a major risk factor for development and progression of NAFLD and weight loss is an effective intervention for the management of NAFLD. However, few patients achieve substantial and sustained weight loss with lifestyle measures. Therefore, antiobesity agents are frequently considered in patients with NAFLD but there are limited data on their safety and efficacy. In the present review, we discuss the role of antiobesity agents in the management of NAFLD. All approved antiobesity agents appear to reduce transaminase levels and to improve steatosis in patients with NAFLD. However, their effects on fibrosis are less well studied and whether they affect liver-related outcomes, including progression to cirrhosis and hepatocellular cancer, is unknown. The glucagon-like peptide-1 receptor agonists, liraglutide and semaglutide, appear to represent a first-line option in obese patients with NAFLD and type 2 diabetes mellitus (T2DM) since they induce considerable weight loss and have been extensively studied in patients with T2DM. However, more studies are needed to evaluated their effects on liver-related and cardiovascular outcomes in patients with NAFLD, particularly in those without T2DM.
Correlations between elevated basal sperm DNA fragmentation and the clinical outcomes in women undergoing IUI
Authors: Zhu Chunhui , Zhang Shengmin , Chen Fang , She Hong , Ju Yun , Wen Xidong , Ji Yurong , Pan Yu , Yang Chunxia , Sun Yan , Dong Naijun , Liu Kaifeng , Li Feng , Xue Tongmin , Cui Hengmi
Published: September 2022

Objective

This study aimed to explore the impact of the sperm DNA fragmentation index (DFI) on the clinical outcomes in women undergoing artificial insemination by husband intrauterine insemination (AIH-IUI).

Methods

In this retrospective study, the value of sperm DFI was detected by sperm chromatin structure assay (SCSA) in a semen analysis collected before fertility treatment (basal DFI) in 1,500 IUI cycles at the infertility clinic of Northern Jiangsu People’s Hospital Reproductive Medicine Center from Jan 2016 to April 2021. Receiver operating characteristic (ROC) curves were used to calculate the cut-off value for the clinical outcomes of IUI, including the biochemical pregnancy rate, clinical pregnancy rate, delivery rate, and live birth rate, and multivariate logistic regression was conducted to analyse the risk factors for clinical outcomes after IUI.

Result

In 1,500 IUI cycles, the results showed that there were no statistically significant differences between the normal DFI group and the abnormal DFI group in biochemical pregnancy rate (14.41% vs. 11.3%, P = 0.386), clinical pregnancy rate (12.9% vs. 10.5%, P = 0.433), delivery rate (11.0% vs. 8.9%, P = 0.456), live birth rate (10.9% vs. 8.9%, P = 0.484) or pregnancy loss rate (14.6% vs. 15.4%, P = 1.000).

Conclusion

Sperm DFI alone may have limited predictive power for IUI clinical outcomes.
Energy Management in Buildings: Lessons Learnt for Modeling and Advanced Control Design
Authors: Rastegarpour Soroush , Ferrarini Luca
Published: September 2022

This paper presents a comparative analysis of different modeling and control techniques that can be used to tackle the energy efficiency and management problems in buildings. Multiple resources are considered, from generation to storage, distribution and delivery. In particular, it is shown what are the real needs and advantages of adopting different techniques, based on different applications, type of buildings, boundary conditions. This contribution is based widely on the experience performed by the authors in the recent years in dealing with existing residential, commercial and tertiary filed buildings, with application ranging from local temperature control up to smart grids where buildings are seen as an active node of the grid thanks to their ability to shape the thermal and electrical profile in real time. As for control models, a wide range of modeling techniques are here investigated and compared, from linear time-invariant models, to time-varying, to nonlinear ones. Similarly, control techniques include adaptive ones and real-time predictive ones.
Evaluation of steam supply performance: Steamer vs. bubbler
Authors: Zhang Yongliang , Xu Nansheng , Tang Qiming , Gibbons William , Huang Kevin
Published: September 2022

Water/steam electrolysis is a key enabling technology for clean, low-carbon and sustainable production of hydrogen and will play a crucial role in future hydrogen economy. For high temperature solid oxide electrolytic cells, steam is the chemical feedstock. A stable and accurate supply of steam to solid oxide electrolytic cells is of vital importance to smooth production of hydrogen. In this study, we compare steam supply performance of two commonly used steam generators: steamer and bubbler. Our results show that bubbler with proper volume and fritted inlet gas tubing can provide more stable and accurate steam supply than steamer for laboratory use. We also provide the explanation for the unstable steam supply observed in steamer. Overall, we conclude that bubbler is generally a better choice for small-scale laboratory use (e.g., ≤50%H2O, ≤100 sccm carrier gas flow) to produce stable and accurate steam and steamer might be a better choice for higher steam contents and flow rates (e.g., >60% H2O and >200) encountered in large-scale testing and/or aggressive high steam conditions.
The role of knowledge about water consumption in the context of intentions to use IoT water metrics
Authors: Madias Konstantinos , Borusiak Barbara , Szymkowiak Andrzej
Published: September 2022

Technological progress can contribute to a more conscious and sustainable consumption of water. This is especially important in the context of dwindling resources and climate change. The objective of the study is to investigate how consumers’ perceived knowledge on water usage influences their intention to adopt smart (IoT-based) water meters, which deliver very precise data on the amount of water used in a household. We hypothesized that perceived knowledge on personal water usage exerts a direct and indirect influence on the intention to adopt a smart water meter. For the mediators, we used the intention to save water and variables derived from Value-Belief-Norm theory: awareness of consequences, ascription of responsibility and personal norm. We verified the hypotheses by applying structural equation modelling to a sample of 532 respondents. We found that perceived knowledge on water usage directly influences the intention to adopt a smart water meter, and that all considered variables worked to mediate the relationship between perceived knowledge and intention. Thus, based on our results perceived knowledge plays an important role on the relationship between values-beliefs-norms and intentions to apply smart water meters, which can be used for future research in order to reduce household water consumption by increasing the probability of installing smart water meters.
Spatial distribution and ecological risk assessment of heavy metals in manganese (Mn) contaminated site
Authors: Lv Yangtao , Kabanda Gilbert , Chen Yueru , Wu Chuan , Li Waichin
Published: September 2022

The spatial distribution, migration characteristics, and ecological risks of heavy metals in manganese (Mn) contaminated sites were studied by field investigation and geostatistical analysis. In this study, surface soil samples were collected from an Mn mine wasteland and the soil in this area was polluted by Mn, Pb, Cu, Cd, Zn, and Cr, and the corresponding element concentrations were 16.3, 15.4, 15.0, 9.90, 6.10, and 1.1 times of the limited standard, respectively. In addition, the soil in different samples in the same region has obvious heterogeneity. By using X-ray fluorescence spectrometry (XRF) and inductively coupled plasma-mass spectrometry (ICP-MS), the heavy metal concentrations in soil samples were determined. ICP-MS corroborated XRF for soil heavy metal determination and showed that XRF was a reliable and quick alternative for heavy metal determination in soil. To discover heavy metal distribution trends, distribution maps of heavy metals were created using the Kriging interpolation method. The geoaccumulation index (Igeo), improved Nemerow index (INI), and potential ecological risk index (RI) was used to assess the pollution degree and the environmental risk of metal pollution in the study area. The contamination degree of heavy metal is Mn > Cd > Pb > Zn > Cu > Cr. The spatial distribution and risk assessment of heavy metals in manganese contaminated sites will help to monitor the migration trajectory of heavy metals in mining areas and protect the soil from long-term accumulation of heavy metals. It provides the basis for heavy metal pollution remediation strategy and ecological risk management.
Effect of tillage management on the wind erosion of arable soil in the Chinese Mollisol region
Authors: Chen Shuai , Zhang Xingyi , Li Jianye , Guo Mingming , Hu Wei
Published: September 2022

Wind erosion is a serious problem in agricultural regions and threatens the regional food production in Northeast China. However, limited information is available on the characteristics of wind erosion in arable soil in Northeast China. As a result, field-based research during periods of vulnerability to wind erosion is essential. This study quantified the characteristics of soil wind erosion under no-tillage (NT) and conventional tillage (CT) treatments in China’s northern “corn-belt.” The results determined the wind erosion transport mode of Mollisols to be generally characterized by creep and supplemented by saltation and suspension in Northeast China. The erodible particles of the creep accounted for 80.37% and 85.42% of the total wind erosion under the NT and CT treatments, respectively. During experiments with erodible particles in the saltation mode from the soil surface to 2 m, the majority of the particles were collected by the sampler at 0.5 m height, with the NT and CT treatments collecting 5.82 kg·m−2 and 6.93 kg·m−2 of erodible particles per unit area, respectively. Wind erosion on agricultural land was observed to be influenced by tillage practices, rainfall, wind speed, and soil moisture content. Average and maximum wind speeds exhibited significant positive correlations with wind erosion during April and May. Moreover, the erodible particles of each wind erosion transport mode (creep, saltation, and suspension) under CT were higher (1.73, 1.41, and 1.35 times) than those under the NT treatment. With less damage and greater protection of the surface soil, the NT treatment was able to decrease the occurrence of wind erosion and influence its outcome on farmland. Therefore, NT treatment should be encouraged as a key initiative for the reduction of wind erosion of arable soil in the Chinese Mollisol region.
Spatial-temporal dynamics and evolution of ecological security in a rapid urbanization city, Southwest China
Authors: Dai Yunchuan , Diao Yuying , Dai Chongyang , Li Yi , Sun Guiyan , Zahoor Babar , Li Dayong
Published: September 2022

The main goal of constructing ecological security patterns (ESPs) is to identify ecological sources, corridors and nodes that play significant roles in sustainable development on a regional scale. Although there are many studies on the construction of ESPs, there is no consensus in terms of research methodology and systematic frameworks for integrated landscape management. Based on land use data from 2000, 2010, and 2020 of Chongqing Municipality in southwest China, we evaluated the spatial-temporal variation of ESPs by integrating InVEST and Circuit Theory. Results showed that: (a) Habitat quality varied through space, with habitat quality being lower in the western and central regions and higher in the southeastern and northeastern regions. (b) The area of lower quality habitat across different time periods was more than 46%, and habitat quality over the last two decades has generally been low with no significant improvement. (c) From 2000 to 2020, ecological sources were primarily distributed in the mountainous areas with high habitat quality and fractional vegetation coverage in the northeast and southeast. The regions identified ecological sources in 2000, 2010, and 2020 accounted for 31.37, 33.53, and 32.7% of Chongqing Municipality, respectively. (d) The ESPs were composed of ecological sources dominated by forests, connected by continuous ecological corridors. The current ESPs of Chongqing Municipality included 20 ecological nodes, 17 continuous ecological corridors and 23 ecological sources. We strongly suggest the local governments strengthen the protection of the identified ecological nodes, ecological corridors, ecological sources, and protection gaps, and focus on strengthening the construction and management of the ecological corridor network system to promote species diffusion and gene exchange. Our findings are helpful for policy makers to introduce appropriate measures to objectively guide urban expansion via rational and sustainable development of land resources and improve the level of ecological security for Chongqing Municipality.
MicroRNA-mediated regulation of key signaling pathways in hepatocellular carcinoma: A mechanistic insight
Authors: Ruiz-Manriquez Luis M. , Carrasco-Morales Oscar , Sanchez Z E. Adrian , Osorio-Perez Sofía Madeline , Estrada-Meza Carolina , Pathak Surajit , Banerjee Antara , Bandyopadhyay Anindya , Duttaroy Asim K. , Paul Sujay
Published: September 2022

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. The molecular pathogenesis of HCC varies due to the different etiologies and genotoxic insults. The development of HCC is characterized by complex interactions between several etiological factors that result in genetic and epigenetic changes in proto-onco and/or tumor suppressor genes. MicroRNAs (miRNAs) are short non-coding RNAs that also can act as oncomiRs or tumor suppressors regulating the expression of cancer-associated genes post-transcriptionally. Studies revealed that several microRNAs are directly or indirectly involved in cellular signaling, and dysregulation of those miRNAs in the body fluids or tissues potentially affects key signaling pathways resulting in carcinogenesis. Therefore, in this mini-review, we discussed recent progress in microRNA-mediated regulation of crucial signaling networks during HCC development, concentrating on the most relevant ones such as PI3K/Akt/mTOR, Hippo-YAP/TAZ, and Wnt/β-catenin, which might open new avenues in HCC management.
Molecular subtype identification and predictive power of N6-methyladenosine regulator in unexplained recurrent pregnancy loss
Authors: Huo Jiahui , Chen Qian , Zhang Yutong , Li Nuo , Fu Zhiyu , Ma Ning , Zheng Nan , Cui Nan , Li Lu
Published: September 2022

The etiology of recurrent pregnancy loss (RPL) is complicated and effective clinical preventive measures are lacking. Identifying biomarkers for RPL has been challenging, and to date, little is known about the role of N6-methyladenosine (m6A) regulators in RPL. Expression data for m6A regulators in 29 patients with RPL and 29 healthy controls were downloaded from the Gene Expression Omnibus (GEO) database. To establish a diagnostic model for unexplained RPL, differential gene expression analysis was conducting for 36 m6A regulators using least absolute shrinkage and selection operator (LASSO) regression. Unsupervised cluster analysis was conducted on hub genes, and probable mechanisms were explored using gene set enrichment analysis (GSEA) and gene ontology (GO) analysis. Correlations between m6A-related differentially expressed genes and immune infiltration were analyzed using single-sample GSEA. A total of 18 m6A regulators showed significant differences in expression in RPL: 10 were upregulated and eight were downregulated. Fifteen m6A regulators were integrated and used to construct a diagnostic model for RPL that had good predictive efficiency and robustness in differentiating RPL from control samples, with an overall area under the curve (AUC) value of 0.994. Crosstalk was identified between 10 hub genes, miRNAs, and transcription factors (TFs). For example, YTHDF2 was targeted by mir-1-3p and interacted with embryonic development-related TFs such as FOXA1 and GATA2. YTHDF2 was also positively correlated with METTL14 (r = 0.5983, p < 0.001). Two RPL subtypes (Cluster-1 and Cluster-2) with distinct hub gene signatures were identified. GSEA and GO analysis revealed that the differentially expressed genes were mainly associated with immune processes and cell cycle signaling pathway (normalized enrichment score, NES = -1.626, p < 0.001). Immune infiltration was significantly higher in Cluster-1 than in Cluster-2 (p < 0.01). In conclusion, we demonstrated that m6A modification plays a critical role in RPL. We also developed and validated a diagnostic model for RPL prediction based on m6A regulators. Finally, we identified two distinct RPL subtypes with different biological processes and immune statuses.
Roles of AIM2 Gene and AIM2 Inflammasome in the Pathogenesis and Treatment of Psoriasis
Authors: Wang Jieyi , Gao Jing , Huang Cong , Jeong Sohyun , Ko Randy , Shen Xue , Chen Chaofeng , Zhong Weilong , Zou Yanfen , Yu Bo , Shen Changbing
Published: September 2022

Psoriasis is an immune-mediated chronic inflammatory skin disease caused by a combination of environmental incentives, polygenic genetic control, and immune regulation. The inflammation-related gene absent in melanoma 2 (AIM2) was identified as a susceptibility gene for psoriasis. AIM2 inflammasome formed from the combination of AIM2, PYD-linked apoptosis-associated speck-like protein (ASC) and Caspase-1 promotes the maturation and release of inflammatory cytokines such as IL-1β and IL-18, and triggers an inflammatory response. Studies showed the genetic and epigenetic associations between AIM2 gene and psoriasis. AIM2 gene has an essential role in the occurrence and development of psoriasis, and the inhibitors of AIM2 inflammasome will be new therapeutic targets for psoriasis. In this review, we summarized the roles of the AIM2 gene and AIM2 inflammasome in pathogenesis and treatment of psoriasis, hopefully providing a better understanding and new insight into the roles of AIM2 gene and AIM2 inflammasome in psoriasis.
Cross-talk of four types of RNA modification proteins with adenosine reveals the landscape of multivariate prognostic patterns in breast cancer
Authors: Wang Xuliren , Ye Fangdie , Xiong Min , Xiu Bingqiu , Chi Weiru , Zhang Qi , Xue Jingyan , Chen Ming , Zhang Liyi , Wu Jiong , Chi Yayun
Published: September 2022

Background: Breast cancer (BC) is the most common malignant tumour, and its heterogeneity is one of its major characteristics. N6-methyladenosine (m6A), N1-methyladenosine (m1A), alternative polyadenylation (APA), and adenosine-to-inosine (A-to-I) RNA editing constitute the four most common adenosine-associated RNA modifications and represent the most typical and critical forms of epigenetic regulation contributing to the immunoinflammatory response, tumorigenesis and tumour heterogeneity. However, the cross-talk and potential combined profiles of these RNA-modified proteins (RMPs) in multivariate prognostic patterns of BC remain unknown.

Methods: A total of 48 published RMPs were analysed and found to display significant expression alterations and genomic mutation rates between tumour and normal tissues in the TCGA-BRCA cohort. Data from 4188 BC patients with clinical outcomes were downloaded from the Gene Expression Omnibus (GEO), the Cancer Genome Atlas (TCGA), and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), normalized and merged into one cohort. The prognostic value and interconnections of these RMPs were also studied. The four prognosis-related genes (PRGs) with the greatest prognostic value were then selected to construct diverse RMP-associated prognostic models through univariate Cox (uniCox) regression analysis, differential expression analysis, Least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox (multiCox) regression. Alterations in biological functional pathways, genomic mutations, immune infiltrations, RNAss scores and drug sensitivities among different models, as well as their prognostic value, were then explored.

Results: Utilizing a large number of samples and a comprehensive set of genes contributing to adenosine-associated RNA modification, our study revealed the joint potential bio-functions and underlying features of these diverse RMPs and provided effective models (PRG clusters, gene clusters and the risk model) for predicting the clinical outcomes of BC. The individuals with higher risk scores showed poor prognoses, cell cycle function enrichment, upregulation of stemness scores, higher tumour mutation burdens (TMBs), immune activation and specific drug resistance. This work highlights the significance of comprehensively examining post-transcriptional RNA modification genes.

Conclusion: Here, we designed and verified an advanced forecasting model to reveal the underlying links between BC and RMPs and precisely predict the clinical outcomes of multivariate prognostic patterns for individuals.
Potential epigenetic molecular regulatory networks in ocular neovascularization
Authors: Hu Qiang , Zhang Xue , Sun Minghao , jiang Bo , Zhang Zhongyu , Sun Dawei
Published: September 2022

Neovascularization is one of the many manifestations of ocular diseases, including corneal injury and vascular diseases of the retina and choroid. Although anti-VEGF drugs have been used to effectively treat neovascularization, long-term use of anti-angiogenic factors can cause a variety of neurological and developmental side effects. As a result, better drugs to treat ocular neovascularization are urgently required. There is mounting evidence that epigenetic regulation is important in ocular neovascularization. DNA methylation and histone modification, non-coding RNA, and mRNA modification are all examples of epigenetic mechanisms. In order to shed new light on epigenetic therapeutics in ocular neovascularization, this review focuses on recent advances in the epigenetic control of ocular neovascularization as well as discusses these new mechanisms.
Detection of four rare thalassemia variants using Single-molecule realtime sequencing
Authors: Luo Shiqiang , Chen Xingyuan , Zeng Dingyuan , Tang Ning , Yuan Dejian , Liu Bailing , Chen Lizhu , Zhong Qingyan , Li Jiaqi , Liu Yinyin , Chen Jianping , Wang Xiaoyuan , Yan Tizhen
Published: September 2022

Conventional methods for the diagnosis of thalassemia include gap polymerase chain reaction (Gap-PCR), reverse membrane hybridization (RDB), multiplex ligation-dependent probe amplification (MLPA) and Sanger sequencing. In this study, we used single molecule real-time technology (SMRT) sequencing and discovered four rare variants that have not been identified by conventional diagnostic methods for thalassemia. We also performed genotype and phenotype analyses on family members of thalassemia patients. The SMRT technology detected five cases in which the proband had abnormal results by conventional diagnostic methods or inconsistencies between the genotype and phenotype. The variants included two cases of an α-globin gene cluster 27,311 bp deletion, --27.3/αα (hg38 chr16:158664-185974), one case of an HS-40 region 16,079 bp deletion (hg38 chr16:100600-116678), one case of a rearrangement of -α3.7α1α2 on one allele and one case of a ß-globin gene cluster HBG1-HBG2 4,924 bp deletion (hg38 chr11:5249345-5254268). This study clarified the hematological phenotypes of four rare variants and indicated the application value of SMRT in the diagnosis of rare α-globin and ß-globin gene cluster deletions, gene recombination and deletion breakpoints. The SMRT method is a comprehensive one-step technology for the genetic diagnosis of thalassemia and is particularly suitable for the diagnosis of thalassemia with rare deletions or genetic recombination.
Novel amino acid metabolism‐related gene signature to predict prognosis in clear cell renal cell carcinoma
Authors: Cheng Xiaofeng , Deng Wen , Zhang Zhicheng , Zeng Zhenhao , Liu Yifu , Zhou Xiaochen , Zhang Cheng , Wang Gongxian
Published: September 2022

Background: Amino acid metabolism (AAM) deregulation, an emerging metabolic hallmark of malignancy, plays an essential role in tumour proliferation, invasion, and metastasis. However, the expression of AAM-related genes and their correlation with prognosis in clear cell renal cell carcinoma (ccRCC) remain elusive. This study aims to develop a novel consensus signature based on the AAM-related genes.

Methods: The RNA-seq expression data and clinical information for ccRCC were downloaded from the TCGA (KIRC as training dataset) and ArrayExpress (E-MTAB-1980 as validation dataset) databases. The AAM‐related differentially expressed genes were screened via the “limma” package in TCGA cohorts for further analysis. The machine learning algorithms (Lasso and stepwise Cox (direction = both)) were then utilised to establish a novel consensus signature in TCGA cohorts, which was validated by the E-MTAB-1980 cohorts. The optimal cutoff value determined by the “survminer” package was used to categorise patients into two risk categories. The Kaplan-Meier curve, the receiver operating characteristic (ROC) curve, and multivariate Cox regression were utilised to evaluate the prognostic value. The nomogram based on the gene signature was constructed, and its performance was analysed using ROC and calibration curves. Gene Set Enrichment Analysis (GSEA) and immune cell infiltration analysis were conducted on its potential mechanisms. The relationship between the gene signature and key immune checkpoint, N6-methyladenosine (m6A)-related genes, and sensitivity to chemotherapy was assessed.

Results: A novel consensus AMM‐related gene signature consisting of IYD, NNMT, ACADSB, GLDC, and PSAT1 is developed to predict prognosis in TCGA cohorts. Kaplan-Meier survival shows that overall survival in the high-risk group was more dismal than in the low-risk group in the TCGA cohort, validated by the E-MTAB-1980 cohort. Multivariate regression analysis also demonstrates that the gene signature is an independent predictor of ccRCC. Immune infiltration analysis highlighted that the high-risk group indicates an immunosuppressive microenvironment. It is also closely related to the level of key immune checkpoints, m6A modification, and sensitivity to chemotherapy drugs.

Conclusion: In this study, a novel consensus AAM-related gene signature is developed and validated as an independent predictor to robustly predict the overall survival from ccRCC, which would further improve the clinical outcomes.
Identifying celiac disease-related chemicals by transcriptome-wide association study and chemical-gene interaction analyses
Authors: Lu Mengnan , Feng Ruoyang , Liu Yuesheng , Qin Yujie , Deng Hongyang , Xiao Yanfeng , Yin Chunyan
Published: September 2022

Celiac disease (CeD) is one of the most common intestinal inflammatory diseases, and its incidence and prevalence have increased over time. CeD affects multiple organs and systems in the body, and environmental factors play a key role in its complex pathogenesis. Although gluten exposure is known to be the causative agent, many unknown environmental factors can trigger or exacerbate CeD. In this study, we investigated the influence of genetic and environmental factors on CeD. Data from a CeD genome-wide association study that included 12,041 CeD cases and 12,228 controls were used to conduct a transcriptome-wide association study (TWAS) using FUSION software. Gene expression reference data were obtained for the small intestine, whole blood, peripheral blood, and lymphocytes. We performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses using the significant genes identified by the TWAS and conducted a protein–protein interaction network analysis based on the STRING database to detect the function of TWAS-identified genes for CeD. We also performed a chemical-related gene set enrichment analysis (CGSEA) using the TWAS-identified genes to test the relationships between chemicals and CeD. The TWAS identified 8,692 genes, including 101 significant genes (padjusted < 0.05). The CGSEA identified 2,559 chemicals, including 178 chemicals that were significantly correlated with CeD. This study performed a TWAS (for genetic factors) and CGSEA (for environmental factors) and identified several CeD-associated genes and chemicals. The findings expand our understanding of the genetic and environmental factors related to immune-mediated diseases.
Adipokines, and not vitamin D, associate with antibody immune responses following dual BNT162b2 vaccination within individuals younger than 60 years
Authors: Pavel-Tanasa Mariana , Constantinescu Daniela , Cianga Corina Maria , Anisie Ecaterina , Mereuta Ana Irina , Tuchilus Cristina Gabriela , Cianga Petru
Published: September 2022

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) led to a global health outbreak known as the COVID-19 pandemic which has been lasting since March 2020. Vaccine became accessible to people only at the beginning of 2021 which greatly helped reducing the mortality rate and severity of COVID-19 infection afterwards. The efficacy of vaccines was not fully known and studies documenting the immune responses following vaccination are continuing to emerge. Recent evidence indicate that natural infection prior vaccination may improve the antibody and cellular immune responses, while little is known about the factors influencing those processes. Here we investigated the antibody responses following BNT162b2 vaccination in relation to previous-infection status and age, and searched for possible biomarkers associated with the observed changes in immune responses. We found that the previous-infection status caused at least 8-times increase in the antibody titres, effect that was weaker in people over 60 years old and unaltered by the vitamin D serum levels. Furthermore, we identified adiponectin to positively associate with antibody responses and negatively correlate with pro-inflammatory molecules (MCP-1, factor D, CRP, PAI-1), especially in previously-infected individuals.
Dysbiosis of human tumor microbiome and aberrant residence of Actinomyces in tumor-associated fibroblasts in young-onset colorectal cancer
Authors: Xu Zhuoqing , Lv Zeping , Chen Fangqian , Zhang Yuchen , Xu Zifeng , Huo Jianting , Liu Wangyi , Yu Suyue , Tuersun Abudumaimaitijiang , Zhao Jingkun , Zong Yaping , Shen Xiaonan , Feng Wenqing , Lu Aiguo
Published: September 2022

Colorectal cancer (CRC) is the third most common form of cancer, and the incidence of sporadic young-onset colorectal cancer (yCRC) has been increasing. Microbiota residing in the tumor microenvironment are emerging tumor components. The colonic microbiome differs between patients with CRC and healthy controls; however, few studies have investigated the role of the tumor microbiota in disease diagnosis and tumorigenesis of yCRC. We performed 16S rRNA sequencing analysis to identify the microbiome in CRC and found that tumor microbial diversity decreased in yCRC. Proteobacteria and Firmicutes were the most abundant phyla in all CRC samples, and Actinomyces and Schaalia cardiffensis were the key microbiota in the yCRC group. Correlation analysis revealed that Actinomyces co-occurred with various pro-tumor microbial taxa, including Bacteroidia, Gammaproteobacteria, and Pseudomonas. An independent cohort was used to validate the results. The Actinomyces in CRC was co-localized with cancer-associated fibroblasts and activated the TLR2/NF-κB pathway and reduces CD8+ T lymphocyte infiltration in CRC microenvironment. This study suggests that tumoral microbiota plays an important role in promoting tumorigenesis and therefore has potential as a promising non-invasive tool and intervention target for anti-tumor therapy.
High-throughput sequencing unravels the cell heterogeneity of cerebrospinal fluid in the bacterial meningitis of children
Authors: Xiao Haihan , Xiao Haijuan , Zhang Yun , Guo Lingyun , Dou Zhenzhen , Liu Linlin , Zhu Liang , Feng Wenya , Liu Bing , Hu Bing , Chen Tianming , Liu Gang , Wen Tingyi
Published: September 2022

Bacterial meningitis (BM) is a common life-threatening infection in children that occurs in the central nervous system (CNS). The cytologic examination of cerebrospinal fluid (CSF) is a key parameter in the diagnosis of BM, but the heterogeneity of cells in the CSF has not been elucidated, which limits the current understanding of BM neuroinflammation. In this study, CSF samples were collected from a number of BM patients who were in different stages of disease progression. Single-cell RNA-sequencing (scRNA-seq), with additional bulk transcriptome sequencing, was conducted to decipher the characteristics of CSF cells in BM progression. A total of 18 immune cell clusters in CSF were identified, including two neutrophils, two monocytes, one macrophage, four myeloid dendritic cells, five T cells, one natural killer cell, one B cell, one plasmacytoid dendritic cell, and one plasma cell subtype. Their population profiles and dynamics in the initial onset, remission, and recovery stages during BM progression were also characterized, which showed decreased proportions of myeloid cells and increased proportions of lymphoid cells with disease progression. One novel neutrophil subtype, FFAR2+TNFAIP6+ neutrophils, and one novel monocyte subtype, THBS1+IL1B+ monocytes, were discovered, and their quantity changes positively correlated with the intensity of the inflammatory response in the CSF during BM. In addition, the CSF of BM patients with unsatisfactory therapeutic responses presented with different cell heterogeneity compared to the CSF of BM patients with satisfactory therapeutic responses, and their CSF featured altered intercellular communications and increased proportions of type II myeloid dendritic cells and plasmacytoid dendritic cells. Moreover, the bulk transcriptome profiles of autologous CSF cells and peripheral blood leukocytes of BM patients showed that the immune cells in these two physiological compartments exhibited distinct immune responses under different onset conditions. In particular, the CSF cells showed a high expression of macrophage characteristic genes and a low expression of platelet characteristic genes compared with peripheral blood leukocytes. Our study conducted an in-depth exploration of the characteristics of CSF cells in BM progression, which provided novel insights into immune cell engagement in acute CNS infection.
Aberrant expansion of follicular helper T cell subsets in patients with systemic lupus erythematosus
Authors: Jin Xin , Chen Jia , Wu Jian , Lu Ying , Li Baohua , Fu Wenning , Wang Wei , Cui Dawei
Published: September 2022

Objective

Systemic lupus erythematosus (SLE) is a chronic and complex autoimmune disease characterized by multiple autoantibodies, resulting in multiple organ and tissue damages. These pathogenic autoantibodies produced by B cells are closely correlated with follicular helper T (Tfh) cell subsets that play a fundamental role in the pathogenesis of SLE. The aim of the present study was to study the phenotype and role of circulating Tfh (cTfh) cell subsets and associated B cell subpopulations in active and inactive SLE patients.

Methods

Thirty SLE outpatients and 24 healthy controls (HCs) were enrolled in this study. The frequency of cTfh cell and B cell subsets in peripheral blood mononuclear cells (PBMCs) and the plasma levels of eight cytokines were determined by flow cytometry, and plasma IL-21 levels were measured by ELISA. Meanwhile, we used MRL/lpr mice as the model of SLE to research the alterations of Tfh cells in the thymus and spleen of mice.

Results

Frequencies of CD4+CXCR5+CD45RA-effector cTfh cells, PD1+cTfh, PD1+ICOS+cTfh, PD1+cTfh1, PD1+cTfh2, PD1+cTfh17, and PD1+ICOS+cTfh1 cells as well as plasmablasts showed significant differences among HC, active and inactive SLE patients. Moreover, cytokines typically associated with cTfh cells, including IL-6 and IL-21, were elevated in active SLE patients compared to inactive SLE patients and HCs. Additionally, a positive correlation was observed between PD1+ICOS+ cTfh or PD1+ICOS+ cTfh1 cell frequencies and plasmablasts or IL-21 levels, as well as between plasmablasts. We also found PD1+ICOS+ Tfh cells expansion in both thymus and spleen of MRL/lpr mice, accompanied by increased frequencies in B cells and plasmablasts, meanwhile, cTfh1which expressing IFN-γ was increased in the peripheral blood of MRL/lpr mice.

Conclusion

Tfh cell subsets and plasmablasts may play a fundamental role in the pathogenesis of SLE and may provide potential targets for therapeutic interventions for SLE.
Immune-inflammatory and hypothalamic-pituitary-adrenal axis biomarkers are altered in patients with non-specific low back pain: A systematic review
Authors: Sanabria-Mazo Juan P. , Colomer-Carbonell Ariadna , Carmona-Cervelló Meritxell , Feliu-Soler Albert , Borràs Xavier , Grasa Mar , Esteve Montserrat , Maes Michael , Edo Sílvia , Sanz Antoni , Luciano Juan V.
Published: September 2022

This systematic review aimed to investigate immune-inflammatory and hypothalamic-pituitary-adrenal (HPA) axis biomarkers in individuals with non-specific low back pain (NSLBP) compared to healthy control. The search was performed in five databases until 4 November 2021. Two reviewers independently conducted screenings, data extraction, risk of bias, and methodological quality assessment of 14 unique studies. All studies reported the source of the fluid analyzed: nine studies used serum, two used plasma, one used serum and plasma, and two studies used salivary cortisol. We found preliminary and limited evidence (only one study for each biomarker) of increased levels in growth differentiation factor 15 (GDF-15), interleukin-23 (IL-23), transforming growth factor–beta (TGF-β), and soluble tumor necrosis factor receptor 1 (sTNF-R1) in NSLBP. Inconsistent and limited evidence was identified for interleukin-10 (IL-10). Although C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor–alpha (TNF-α) levels appear to increase in NSLBP, only one study per each biomarker reported statistically significant differences. Interleukin-1 beta (IL-1β), interleukin-17 (IL-17), interferon gamma (IFN-γ), and high-sensitivity CRP (hsCRP) showed no significant differences. Regarding cortisol, one study showed a significant increase and another a significant decrease. More robust evidence between GDF-15, IL-23, TGF-β, and sTNF-R1 with NSLBP is needed. Moreover, contrary to the findings reported in previous studies, when comparing results exclusively with healthy control, insufficient robust evidence for IL-6, TNF-α, and CRP was found in NSLBP. In addition, cortisol response (HPA-related biomarker) showed a dysregulated functioning in NSLBP, with incongruent evidence regarding its directionality. Therefore, our effort is to find adjusted evidence to conclude which immune-inflammatory and HPA axis biomarkers are altered in NSLBP and how much their levels are affected.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020176153, identifier CRD42020176153.
FGFBP1 as a potential biomarker predicting bacillus Calmette–Guérin response in bladder cancer
Authors: Li Fei , Zhang Henghui , Wang Yu , Yao Zhihao , Xie Kunfeng , Mo Qixin , Fan Qin , Hou Lina , Deng Fan , Tan Wanlong
Published: September 2022

Accurate prediction of Bacillus Calmette–Guérin (BCG) response is essential to identify bladder cancer (BCa) patients most likely to respond sustainably, but no molecular marker predicting BCG response is available in clinical routine. Therefore, we first identified that fibroblast growth factor binding protein 1 (FGFBP1) was upregulated in failures of BCG therapy, and the increased FGFBP1 had a poor outcome for BCa patients in the E-MTAB-4321 and GSE19423 datasets. These different expression genes associated with FGFBP1 expression are mainly involved in neutrophil activation, neutrophil-mediated immunity, and tumor necrosis factor-mediated signal pathways in biological processes. A significant positive correlation was observed between FGFBP1 expression and regulatory T-cell (Treg) infiltration by the Spearman correlation test in the BCG cohort (r = 0.177) and The Cancer Genome Atlas (TCGA) cohort (r = 0.176), suggesting that FGFBP1 may influence the response of BCa patients to BCG immunotherapy through immune escape. Though FGFBP1 expression was positively correlated with the expressions of PD-L1, CTLA4, and PDCD1 in TCGA cohort, a strong association between FGFBP1 and PD-L1 expression was only detected in the BCG cohort (r = 0.750). Furthermore, elevated FGFBP1 was observed in BCa cell lines and tissues in comparison to corresponding normal controls by RT-qPCR, Western blotting, and immunohistochemical staining. Increased FGFBP1 was further detected in the failures than in the responders by immunohistochemical staining. Notably, FGFBP1 is positively associated with PD-L1 expression in BCa patients with BCG treatment. To sum up, FGFBP1 in BCa tissue could be identified as a promising biomarker for the accurate prediction of BCG response in BCa.
Construction and characterization of a contagious ecthyma virus double-gene deletion strain and evaluation of its potential as a live-attenuated vaccine in goat
Authors: Zhu Zhen , Qu Guanggang , Du Jige , Wang Changjiang , Chen Yong , Shen Zhanning , Zhou Zhiyu , Yin Chunsheng , Chen Xiaoyun
Published: September 2022

Contagious ecthyma is a highly contagious viral disease with zoonotic significance caused by orf virus (ORFV) that affects domestic, ruminants and humans. Live attenuated virus and attenuated tissue culture vaccines are widely used in the fight against ORFV, however, the conventional attenuated vaccine strains have many drawbacks. The aim of this project was to construct a promising contagious ecthyma vaccine strain with safety, high protection efficacy and accessibility by genetic manipulation to against the disease. Using a natural ORFV-GS14 strain as the parental virus, recombinant virus, rGS14-ΔCBP-ΔGIF, with double deletions in the genes encoding the chemokine binding protein (CBP) and granulocyte/macrophage colony-stimulating factor inhibitory factor (GIF) was generated and characterized in vitro and in vivo. Results showed that the growth kinetics curve of rGS14-ΔCBP-ΔGIF and parental virus was consistent, both reaching plateau phase at 48 h post infection, which indicated that the double deletion of cbp and gif genes had little impact on the replication properties of the recombinant virus in primary goat testis (PGT) cell cultures compared with the parental virus. The safety of the double gene-deleted virus was evaluated in lambs. The lambs were monitored for 21 days post infection of the recombinant virus and no ORFV associated symptoms were observed in 21 days post-infection except for slight fever and anorexia in 5 days post-infection, and all lambs inoculated with either recombinant virus or PBS exhibited no clinical signs. To assess the protection efficacy of the rGS14-ΔCBP-ΔGIF, groups of four lambs each were inoculated with rGS14-ΔCBP-ΔGIF, rGS14-ΔCBP, rGS14-ΔGIF or PBS and challenged by a wild type virulent ORFV strain that was isolated from proliferative scabby lesions tissues of infected goat at 21-day post-inoculation. During 14 days post-challenging, lambs inoculated with rGS14-ΔCBP-ΔGIF all remained healthy with unimmunized group all infected, while the single gene-deleted viruses only protected 40% to 50% animals. These results indicated that the double gene-deleted recombinant virus could provide complete protection against virulent ORFV challenging. In conclusion, the double gene-deleted recombinant virus strain, rGS14-ΔCBP-ΔGIF, would be a promising candidate vaccine strains with safety, high protection efficacy and availability.