bluuebunny/crossref_metadata_2025_split huggingface dataset:
FURIN Promoter Methylation Predicts the Risk of Incident Diabetes: A Prospective Analysis in the Gusu Cohort
Authors: He Yan , Li Yinan , Zhang Jianan , Chen Linan , Li Jing , Zhang Min , Zhang Qiu , Lu Ying , Jiang Jun , Zhang Xiaolong , Hu Jianwei , Ding Yi , Zhang Mingzhi , Peng Hao 
Published: March 2022

BackgroundFurin has been associated with diabetes but the underlying mechanisms are unclear. As a mediator linking fixed genome and dynamic environment, DNA methylation of its coding gene FURIN may be involved. Here, we aimed to examine the prospective association between DNA methylation in FURIN promoter and incident diabetes during 4 years of follow-up in Chinese adults.MethodsDNA methylation levels in FURIN promoter were quantified by target bisulfite sequencing using peripheral blood from 1836 participants in the Gusu cohort who were free of diabetes at baseline. To examine the association between DNA methylation levels in FURIN promoter and incident diabetes, we constructed a logistic regression model adjusting for the conventional factors. Multiple testing was controlled by adjusting for the total number of CpG sites assayed using the false-discovery rate approach.ResultsAmong the 1836 participants free of diabetes at baseline, 109 (5.94%) participants developed diabetes during the average of 4 years of follow-up. Hypermethylation at two of the eight CpG sites assayed in the FURIN promoter was associated with an increased risk of diabetes, after multivariable adjustment and multiple testing correction. Every 5% increment in methylation levels at CpG1 and CpG2 were associated with a 22% (OR=1.22, 95%CI: 1.05-1.43, P=0.009, q=0.038) and 39% (OR=1.39, 95%CI: 1.08-1.77, P=0.009, q=0.038) higher risk of incident diabetes, respectively. The gene-based association analysis revealed that DNA methylation at multiple CpG loci was jointly associated with incident diabetes (P&lt;0.001). Using the average methylation level of the 8 CpG loci in FURIN promoter revealed a similar association (OR=1.28, 95% CI: 1.02–1.62, P=0.037).ConclusionsThese results suggested that the hypermethylation levels in FURIN promoter were associated with an increased risk for incident diabetes in Chinese adults.
Development and Application of an Aerosol Model Under a Severe Nuclear Accident
Authors: Yuan Xianbao , Wei Jingyu , Zhang Binhang , Guo Yuefeng , Shi Qiang , Guo Pan , Yang Senquan , Tan Chao 
Published: March 2022

Radioactive aerosol will transport in the containment and also will leak into the environment under a severe nuclear accident. Thus, it is of great significance for predicting the behavior of aerosol under a severe nuclear accident. In order to analyze the aerosol behavior, an improved multi-component sectional model is developed, which improves section numbers and updates the aerosol particle density at each time step. The model’s dependability is confirmed to use benchmark and experimental values. An excellent agreement can be observed between simulation and benchmark. On this premise, the LBLOCA accident is chosen to explore the behavior of radioactive aerosol in the containment. The finding shows that the aerosol is mostly deposited on the structure’s surface due to gravity in the LBLOCA accident. According to a comparison of the influence of aerosol natural deposition mechanisms on the distribution of diameter particles, Brownian diffusion, thermophoresis, diffusiophoresis, and gravity all have an effect on aerosol in the range of 0.01 μm–0.03 μmparticles, and the deposition of 2 μm–20 μmparticles is mainly due to gravity. After comparing and evaluating the influence of aerosol density in the containment, it can be inferred that changed aerosol particle density leads aerosol particles coagulate into larger particles.
A Positive Climatic Trend in the Global Offshore Wind Power
Authors: Zheng Chong-wei , Yi Cheng-tao , Shen Chong , Yu De-chuan , Wang Xiao-lu , Wang Yong , Zhang Wen-kai , Wei Yong , Chen Yun-ge , Li Wei , Jin Xin , Jia Shuai-dong , Wu Di , Wei Ding-jiang , Zhao Xiao-feng , Tian Yan-yan , Zhou Wen , Xiao Zi-niu 
Published: March 2022

The climatic variation of offshore wind energy has a close relationship with the long-term plan of energy utilization. However, the work on this aspect is scarce and mainly focuses on the variation of wind power density (WPD). There is little research on the climatic trends of effective wind speed occurrence (EWSO) and occurrence of energy level greater than 200 W/m2 (rich level occurrence, RLO), which are directly related to the available rate and richness of wind energy. Based on the ERA-Interim wind product from the ECMWF, this study calculated the climatic trends of series of key factors of wind energy in the global oceans, including the WPD, EWSO, and RLO. The results show that the wind energy exhibits a positive trend globally for the past 36 years, with overall annual increasing trends in WPD, EWSO, and RLO, of 0.698 (W/m2)/yr, 0.076%/yr, and 0.090%/yr separately. The annual trend exhibits evident regional differences. The areas with significant increasing trends are mainly distributed in the mid- low-latitude waters of global oceans and part of the southern hemisphere westerlies. The annual increasing trend of WPD is strongest in the southern westerlies, especially in the extratropical South Pacific (ETSP), of about 1.64 (W/m2)/yr. The annual increasing trends of EWSO and RLO are strongest in the tropical waters, especially the tropical Pacific Ocean (TPO), of 0.17%/yr and 0.19%/yr separately. The annual and seasonal WPD, EWSO, and RLO in most global oceans have significant increasing trends or no significant variation, meaning that the wind energy trends are rich or stable, which is beneficial for energy development. The climatic trends of wind energy are dominated by different time periods. There is no evident abrupt change of wind energy in the extratropical waters globally and tropical Atlantic Ocean (TAO). The abrupt periods of wind energy in the TIO and TPO occurred in the end of the 20th century and the beginning of the 21st century. The wind energy of the South China Sea, Arabian Sea, and the Bay of Bengal and nino3 index share a common period of approximately 5 years. The offshore wind energy was controlled by an oscillating phenomenon.
Sensory Disturbance by Six Insecticides in the Range of μg/L in Caenorhabditis elegans
Authors: Zhou Rong , Yu Yue , Zhang Weidong , Wang Dayong , Bai Yanan , Wang Yixuan , Bu Yuanqing 
Published: March 2022

Using Caenorhabditis elegans as an animal model, the possible toxic effects of six insecticides (dinotefuran, thiamethoxam, thiacloprid, nitenpyram, acetamiprid, and sulfoxaflor) commonly used in agriculture on sensory perception were examined. The sensory behaviors of thermotaxis, avoidance of copper ion, chemotaxis to NaCl, and chemotaxis to diacetyl were measured to investigate the damage on sensory perceptions in nematodes exposed to the examined insecticides in the range of micrograms per liter (μg/L). Exposure to dinotefuran, thiamethoxam, thiacloprid, nitenpyram, acetamiprid, or sulfoxaflor at concentrations of 10–100 μg/L resulted in severe deficits in sensory perceptions to temperature, copper ion, NaCl, and diacetyl. The relative neurotoxicity of the six insecticides examined to C. elegans were shown as dinotefuran &gt; thiamethoxam &gt; thiacloprid &gt; nitenpyram &gt; acetamiprid &gt; sulfoxaflor. Moreover, post-treatment with the antioxidant ascorbate effectively suppressed the production of reactive oxygen species and damages of sensory perceptions induced by the six insecticides, indicating that the activation of oxidative stress can act as an important cellular contributor to the observed damage of the examined insecticides in affecting sensory perceptions. Our data highlighted the potential toxicity of the six insecticides at low concentrations in inducing sensory disturbance to environmental organisms.
Non-Lethal Blood Sampling of Fish in the lab and Field With Methods for Dried Blood Plasma Spot Omic Analyses
Authors: Pollard S , Anderson JC , Bah F , Mateus M , Sidhu M , Simmons DBD 
Published: March 2022

There is global acknowledgment that humane methods in animal research are a priority, but few environmental effects monitoring programs use nonlethal methods for fish. The goal of the present study was to determine the impacts of sampling small volumes of blood in larger-bodied fish on survival and healing. In addition to evaluating survival following blood sampling, we evaluated the utility of dried blood spots as an alternative for sample processing and storage in the field. In our approach, we housed 80 rainbow trout (Oncorhynchus mykiss) in our flow-through aquatic facility. We then anaesthetized using MS-222 and sampled 1 μl/g bw of blood via puncture of the caudal vasculature. We tested four different post-blood sampling treatments on the puncture wound: 1. application of liquid bandage; 2. a swab of betadine; 3. a swab of fish mucous; and 4. compared survival outcomes to a group where no post-treatment was performed (negative control). Overall, we observed 90% survival among all treatments, with the most effective approach being the negative control (100% survival). Based upon these results, we repeated the blood sampling with no-post treatment by housing 20 rainbow trout (not previously tested upon) in cages at a nearby creek and monitored survival for 2 weeks post sampling. The survival rate was 95% with full healing of the puncture site in all subjects. In addition to this, we tested the efficacy of dry blood spotting on proteomic, lipidomic and amino acid analysis as an alternative method for blood sample processing and storage. It was found that dried plasma spotting using parafilm in conjunction with a modified Bligh-Dyer extraction offered the best balance for good recovery of protein, lipid and amino acids relative to wet plasma and Noviplex dried plasma spot cards. In this article, we will present the detailed results of these combined studies and describe what we have determined to be the safest non-lethal blood sampling protocol.
Outcome of Hydroxyurea Use in SCD and Evaluation of Patients’ Perception and Experience in Nigeria
Authors: Chianumba Reuben Ikechukwu , Ofakunrin Akinyemi O. D. , Morrice Jack , Olanrewaju Olaniyi , Oniyangi Oluseyi , Kuliya-Gwarzo Aisha , Nnebe-Agumadu Uche , Isa Hezekiah Alkali , Nnodu Obiageli Eunice 
Published: March 2022

Introduction: Hydroxyurea (HU) has been shown to be beneficial in the management of sickle cell disease (SCD) as it improves treatment outcomes. However, despite the benefits of HU, its uptake among SCD patients in Nigeria remains low.Objective: This study aimed to assess the perception and experience of patients with SCD in Nigeria who are using or had used HU, thereby informing and promoting its use.Methodology: A multi-centre, cross-sectional study was conducted among 378 SCD patients aged 1–53 years who have enrolled on Sickle Pan African Research Consortium (SPARCO) registry as HU users. The SPARCO project was funded by the National Institutes of Health (NIH) to establish a sickle cell disease (SCD) registry, strengthen skills and plan research in three African countries. The Nigerian SPARCO registry had 6453 SCD patients at the time of this report with &lt;15% of this population on HU. Data on sociodemographics, perception and experience about HU use were obtained and analysed using descriptive statistics.Findings: Out of the 378 participants, 339 (89.7%) were using HU while 39 (10.3%) had stopped using HU at the time of the study. 281 (74.3%) found HU expensive, while 194 (51.3%) reported none to minimal side effects while using HU. Among patients that stopped HU, cost (59%) and availability (51.3%) were the commonest reasons for discontinuing the drug. Furthermore, 347 (92.5%) had fewer pain crises, 173 (84.8%) had a fewer need for blood transfusion, 145 (86.3%) had improved PCV and 318 (84.6%) had fewer hospital admissions. Finally, the study also showed that 322 (85.2%) respondents would recommend the drug to other patients, whereas 14 respondents (3.7%) would not. Mean corpuscular volume (MCV) and fetal hemoglobin (HbF) levels were not collected in this study and may have improved findings.Conclusion: This study showed that the majority of the SCD patients had good perception and experience with the use of HU while a few had to stop the medication mostly on account of cost and availability. Patients’ based advocacy could be leveraged to improve HU uptake while more efforts are needed to ensure that it is readily available and affordable.
Case Report: Prenatal Diagnosis of a Novel Variant c.251dupT (p.N87Kfs*6) in BCOR Resulting in Oculofaciocardiodental Syndrome Using Whole-Exome Sequencing
Authors: Zhuang Jianlong , Chen Chunnuan , Chen Yu’e , Zeng Shuhong , Jiang Yuying , Wang Yuanbai , Chen Xinying , Xie Yingjun , Wang Gaoxiong 
Published: March 2022

Background: Oculofaciocardiodental (OFCD) syndrome is an X-linked dominant syndrome caused by BCOR variants, which manifests only in females and presumed leading to male lethality. Herein, we aim to present a prenatal diagnosis for OFCD syndrome associated with a novel hemizygous variant in BCOR gene.Case presentation: A 29-year-old pregnant woman from Quanzhou Fujian Province, China, with fetal ultrasound anomalies, was enrolled in this study. A normal 46, XY karyotype with no abnormalities was observed in the fetus detected on microarray. Furthermore, a whole-exome sequencing (WES) detection result demonstrated that a novel hemizygous variant of c.251dupT (p.N87Kfs*6) in the BCOR gene was identified in the fetus, which was a frameshift mutation and classified as a likely pathogenic variant, and may lead to OFCD syndrome according to the clinical feature of the fetus. In this case, male lethality had not occurred by the end of the second trimester, then termination of the pregnancy was conducted at a gestational age of 26 weeks. Sanger sequencing of parental samples revealed that the variant was maternally transmitted, which was consistent with the OFCD syndrome phenotypic features observed in her.Conclusions: In the study, we first present the affected male with a novel variant in BCOR that leads to the OFCD syndrome. Additionally, our study broadened the spectrum of BCOR results in the OFCD syndrome and provided the valuable references for prenatal genetic consultation.
Chromosomal Diversification in Ancistrus Species (Siluriformes: Loricariidae) Inferred From Repetitive Sequence Analysis
Authors: Santos da Silva Kevin , Glugoski Larissa , Vicari Marcelo Ricardo , de Souza Augusto César Paes , Noronha Renata Coelho Rodrigues , Pieczarka Julio Cesar , Nagamachi Cleusa Yoshiko 
Published: March 2022

The Ancistrus genus has extensive chromosomal diversity among species, including heteromorphic sex chromosomes occurrence. However, studies have been shown that chromosomal diversity may still be underestimated. Repetitive sequences represent a large part of eukaryotic genomes, associated with mechanisms of karyotypic diversification, including sex chromosomes evolution. This study analyzed the karyotype diversification of two Ancistrus species (Ancistrus sp. 1 and Ancistrus sp. 2) from the Amazon region by classical and molecular chromosomal markers. Conventional chromosome bands and fluorescence in situ hybridization using probes 18S and 5S rDNA, besides (CA)n, (CG)n, (GA)n, (CAC)n, (CAG)n, (CAT)n, (GAA)n, (GAC)n, (TAA)n, and (TTAGGG)n in tandem repeats were determined on the karyotypes. Ancistrus sp. 1 and Ancistrus sp. 2 presented karyotypes with 2n = 38 (20 m + 14sm+4st, XX/XY) and 2n = 34 (20 m + 14sm, without heteromorphic sex chromosomes), respectively. Robertsonian rearrangements can explain the diploid number difference. C-bands occurred in pericentromeric regions in some chromosomes, and a single 18S rDNA locus occurred in both species. The 5S rDNA showed variation in the number of loci between species karyotypes, suggesting the occurrence of unstable sites and rearrangements associated with these sequences in Ancistrus. The microsatellite mapping evidenced distinct patterns of organization between the two analyzed species, occurring mainly in the sex chromosomes in Ancistrus sp. 1, and in the centromeric and pericentromeric regions of chromosomes m/sm in Ancistrus sp. 2. These data shows the extensive chromosomal diversity of repetitive sequences in Ancistrus, which were involved in Robertsonian rearrangements and sex chromosomes differentiation.
TP53 /KRAS Co-Mutations Create Divergent Prognosis Signatures in Intrahepatic Cholangiocarcinoma
Authors: Guo Chunguang , Liu Zaoqu , Yu Yin , Chen Yunfang , Liu Hui , Guo Yaming , Peng Zhenyu , Cai Gaopo , Hua Zhaohui , Han Xinwei , Li Zhen 
Published: March 2022

Background: Due to high invasiveness and heterogeneity, the morbidity and mortality of intrahepatic cholangiocarcinoma (ICC) remain unsatisfied. Recently, the exploration of genomic variants has decoded the underlying mechanisms of initiation and progression for multiple tumors, while has not been fully investigated in ICC.Methods: We comprehensively analyzed 899 clinical and somatic mutation data of ICC patients from three large-scale cohorts. Based on the mutation landscape, we identified the common high-frequency mutation genes (FMGs). Subsequently, the clinical features, prognosis, tumor mutation burden (TMB), and pharmacological landscape from patients with different mutation carriers were further analyzed.Results: We found TP53 and KRAS were the common FMGs in the three cohorts. Kaplan–Meier survival curves and univariate and multivariate analysis displayed that TP53 and KRAS mutations were associated with poor prognosis. Considering the co-mutation phenomenon of TP53 and KRAS, we stratified patients into “Double-WT,” “Single-Hit,” and “Double-Hit” phenotypes by mutation status. Patients with the three phenotypes showed significant differences in the mutation landscape. Additionally, compared with “Double-WT” and “Single-Hit” phenotypes, patients with “Double-Hit” presented a dismal prognosis and significantly high TMB. Through chemotherapy sensitivity analysis, we identified a total of 30 sensitive drugs for ICC patients, of which 22 were drugs sensitive to “Double-WT,” 7 were drugs sensitive to “Double-Hit,” and only one was a drug sensitive to “Single-Hit.”Conclusion: Our study defined a novel mutation classification based on the common FMGs, which may contribute to the individualized treatment and management of ICC patients.
Relationship Between Programmed Death Ligand 1 Expression and Other Clinicopathological Features in a Large Cohort of Gastric Cancer Patients
Authors: Chen Xinhua , Zhang Huimin , Wang Minghao , Liu Hao , Hu Yanfeng , Lin Tian , Chen Hao , Zhao Mingli , Chen Tao , Li Guoxin , Yu Jiang , Zhao Liying 
Published: March 2022

BackgroundAntibodies against programmed death 1 (PD-1) and its ligand, programmed death-ligand 1 (PD-L1) have recently shown promising results in gastric cancer (GC). However, clinicians still lack predictive biomarkers for the efficacy of anti-PD-1 therapy; thus, we investigated the expression of PD-L1 in GC and further assessed its clinical relevance with other clinicopathological features.MethodsWe retrospectively collected clinical data on 968 consecutive GC cases from Nanfang Hospital between November 2018 and August 2021. Discrepancy in the combined positive score (CPS) of PD-L1 protein expression between gastric mucosa biopsy and postoperative pathology were investigated. Correlations between CPS and clinicopathological parameters were determined using chi-squared test, multiple logistic aggression analysis, and linear regression analysis.ResultsAmong the 968 consecutive GC patients, 199 who did not receive preoperative chemotherapy or immunotherapy were tested for CPS both in gastric mucosa biopsy and postoperative pathology, and the results showed that the CPS of gastric mucosa biopsy was significantly lower than that of postoperative pathology [mean ± SD: 5.5 ± 9.4 vs. 13.3 ± 17.4; M(IQR): 2(5) vs. 5(12), p&lt;0.001)]. 62.3% of patients (579/930) had CPS≥ 1, 49.2% of patients (458/930) had CPS≥5, and 33.3% of patients (310/930) had CPS≥10. Mismatch repair deficiency (dMMR) status was seen in 6.1% of patients (56 of 919). Positive Epstein–Barr virus (EBV) status was detected in 4.4% of patients (38 of 854). The patients with CPS≥1/CPS≥5/CPS≥10 were significantly independently correlated with age, Lauren classification, Ki-67 index, and EBV status. According to linear regression analysis, PD-L1 expression was correlated with age (p&lt;0.001), Ki-67 index (p&lt;0.001), EBV (p&lt;0.001), and Lauren classification (p=0.002).ConclusionsOur results confirmed that PD-L1 expression has Intratumoral heterogeneity in GC. Furthermore, the variables of age, Ki-67 index, and Lauren classification, which are common and accessible in most hospitals, are worth exploring as potential biomarkers for anti-PD-1 therapy in GC.
Electroacupuncture Inhibits NLRP3 Activation by Regulating CMPK2 After Spinal Cord Injury
Authors: Chen Yi , Wu Lei , Shi Mengting , Zeng Danyi , Hu Rong , Wu Xingying , Han Shijun , He Kelin , Xu Haipeng , Shao XiaoMei , Ma Ruijie 
Published: March 2022

ObjectivesThis study aimed to evaluate the expression of cytosine monophosphate kinase 2 (CMPK2) and activation of the NLRP3 inflammasome in rats with spinal cord injury (SCI) and to characterize the effects of electroacupuncture on CMPK2-associated regulation of the NLRP3 inflammasome.MethodsAn SCI model was established in Sprague–Dawley (SD) rats. The expression levels of NLRP3 and CMPK2 were measured at different time points following induction of SCI. The rats were randomly divided into a sham group (Sham), a model group (Model), an electroacupuncture group (EA), an adeno-associated virus (AAV) CMPK2 group, and an AAV NC group. Electroacupuncture was performed at jiaji points on both sides of T9 and T11 for 20 min each day for 3 consecutive days. In the AAV CMPK2 and AAV NC groups, the viruses were injected into the T9 spinal cord via a microneedle using a microscope and a stereotactic syringe. The Basso–Beattie–Bresnahan (BBB) score was used to evaluate the motor function of rats in each group. Histopathological changes in spinal cord tissue were detected using H&amp;E staining, and the expression levels of NLRP3, CMPK2, ASC, caspase-1, IL-18, and IL-1β were quantified using Western blotting (WB), immunofluorescence (IF), and RT-PCR.ResultsThe expression levels of NLRP3 and CMPK2 in the spinal cords of the model group were significantly increased at day 1 compared with those in the sham group (p &lt; 0.05). The expression levels of NLRP3 and CMPK2 decreased gradually over time and remained low at 14 days post-SCI. We successfully constructed AAV CMPK2 and showed that CMPK2 was significantly knocked down following 2 dilutions. Finally, treatment with EA or AAV CMPK2 resulted in significantly increased BBB scores compared to those in the model group and the AAV NC group (p &lt; 0.05). The histomorphology of the spinal cord in the EA and AAV CMPK2 groups was significantly different than that in the model and AAV NC groups. WB, IF, and PCR analyses showed that the expression levels of CMPK2, NLRP3, ASC, caspase-1, IL-18, and IL-1β were significantly lower in the EA and AAV CMPK2 groups compared with those in the model and AAV NC groups (p &lt; 0.05).ConclusionOur study showed that CMPK2 regulated NLRP3 expression in rats with SCI. Activation of NLRP3 is a critical mechanism of inflammasome activation and the inflammatory response following SCI. Electroacupuncture downregulated the expression of CMPK2 and inhibited activation of NLRP3, which could improve motor function in rats with SCI.