Publications by authors named "Wei Dai"

803 Publications

Considerations for Developing a Reassessment Process: Report from the Canadian Real-World Evidence for Value of Cancer Drugs (CanREValue) Collaboration's Reassessment and Uptake Working Group.

Curr Oncol 2021 Oct 16;28(5):4174-4183. Epub 2021 Oct 16.

Temerty Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.

The Canadian Real-world Evidence for Value in Cancer Drugs (CanREValue) Collaboration was established to develop a framework for generating and using real-world evidence (RWE) to inform the reassessment of cancer drugs following initial health technology assessment (HTA). The Reassessment and Uptake Working Group (RWG) is one of the five established CanREValue Working Groups. The RWG aims to develop considerations for incorporating RWE for HTA reassessment and strategies for using RWE to reassess drug funding decisions. Between February 2018 and December 2019, the RWG attended four teleconferences (with follow-up surveys) and two in-person meetings to discuss recommendations for the development of a reassessment process and potential barriers and facilitators. Modified Delphi methods were used to gather input. A draft report of recommendations (to December 2018) was shared for public consultation (December 2019 to January 2020). Initial considerations for developing a reassessment process were proposed. Specifically, reassessment can be initiated by diverse stakeholders, including decision makers from public drug plans or industry stakeholders. The reassessment process should be modelled after existing deliberation and recommendation frameworks used by HTA agencies. Proposed reassessment outcome categories include maintaining status quo, revisiting funding criteria, renegotiating price, or disinvesting. Overall, these initial considerations will serve as the basis for future advancements by the Collaboration.
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http://dx.doi.org/10.3390/curroncol28050354DOI Listing
October 2021

[Determination of plant growth regulators in animal-derived foods using QuEChERS-isotope-labeled internal standards with high performance liquid chromatography-tandem mass spectrometry].

Se Pu 2021 Nov;39(11):1213-1221

Comprehensive Technology Centre of Guiyang Customs, Guiyang 550081, China.

As among the most widely used pesticides in agriculture, plant growth regulators (PGRs) have a positive influence on plants. However, the overuse of PGRs may induce toxicity in food and even be hazardous to human health. Numerous studies have investigated the presence and residues of PGRs on vegetables and fruits. Animal-derived foods are one of the most dominant food sources providing nutrients to fulfil the daily dietary intake, and could also be potentially contaminated by PGRs. However, there is little information on PGR residues in animal-derived foods. Standardization also lacks among the techniques for PGR determination in animal-derived foods, thereby restricting the further establishment of pesticide usage and food safety regulations. Therefore, in this study, a rapid and effective method for analyzing chlormequat chloride, thidiazuron, and paclobutrazol in animal-derived food samples was established. The method primarily involves high performance liquid chromatography-tandem mass spectrometry combined with the use of isotope-labeled internal standards. The extraction and clean-up procedures were based on the QuEChERS method. The analytes were extracted from pork, beef, chicken, pork liver, egg, and milk samples using acetonitrile, followed by 4 g anhydrous magnesium sulfate (MgSO), and 1 g sodium chloride (NaCl). The supernatant was removed using a mixture of 50 mg -propyl ethylenediamine (PSA), 50 mg octadecyl silane (C18), and 150 mg MgSO, and then passed through a 0.22 μm membrane filter before determination. The Agilent ZORBAX Eclipse Plus C18 column (150 mm×3.0 mm, 1.8 μm) was used to separate the analytes under a gradient elution program, with acetonitrile and 5 mmol/L ammonium acetate solution as mobile phases. The analytes were detected by mass spectrometry using the positive and negative electrospray ionization modes under the multiple reaction monitoring mode. Matrix-matched calibration combined with internal standards was used to quantify the PGRs. The linear regression correlation coefficients () for the PGRs were all greater than 0.990 in the corresponding linear concentration ranges. Chlormequat chloride, thidiazuron, and paclobutrazol showed good linearities in the range of 0.1-100 μg/L for the egg and pork liver samples and 0.1-50 μg/L for the pork, beef, and chicken samples. For the milk samples, thidiazuron and paclobutrazol showed good linearities in the range of 0.05-10 μg/L, while chlormequat chloride showed linearity in the range of 0.05-5 μg/L. The limit of detection (LOD) and limit of quantification (LOQ) for each PGR were based on the signal-to-noise () ratios. Under optimal conditions, the LODs ranged from 0.01 μg/kg to 0.1 μg/kg, where the LOD was defined as the amount of the tested compound that generated an ratio higher than 3. In addition, the LOQs were in the range of 0.5-5 μg/kg, with an ratio higher than 10. The precision and accuracy were evaluated by recovery experiments. At the LOQ, twice the LOQ, and 10 times the LOQ, the mean recoveries were in the range of 70.0%-117.4%, and the relative standard deviations (RSDs) ranged from 0.8% to 16.1%. The results indicated that the proposed method is accurate and reliable. This method is a modification of the QuEChERS method, and is advantageous owing to its simplicity and high sensitivity. The use of matrix-matching calibration curves and internal standards can eliminate matrix interference, thereby increasing the accuracy of the method. This method satisfies the testing requirements for chlormequat chloride, thidiazuron, and paclobutrazol residues in animal-derived foods, and is promising for the determination of other PGRs or other types of pesticides in animal-derived foods.
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http://dx.doi.org/10.3724/SP.J.1123.2021.01029DOI Listing
November 2021

ASO Author Reflections: Using Patient-Reported Outcomes to Compare Thoracoscopic Segmentectomy and Lobectomy.

Ann Surg Oncol 2021 Oct 20. Epub 2021 Oct 20.

Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China.

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http://dx.doi.org/10.1245/s10434-021-10948-5DOI Listing
October 2021

Comparing Hypofractionated With Conventional Fractionated Radiotherapy After Breast-Conserving Surgery for Early Breast Cancer: A Meta-Analysis of Randomized Controlled Trials.

Front Oncol 2021 1;11:753209. Epub 2021 Oct 1.

Department of General Surgery, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, China.

Background: The purpose of this meta-analysis was to compare the safety and efficacy between hypofractionated and conventional fractionation radiotherapy in patients with early-stage breast cancer after breast-conserving surgery.

Methods: We conducted a comprehensive search of PubMed, Embase, Web of Science, and the Cochrane Library to identify relevant randomized controlled trials (RCTs) published before February 2021. At the same time, the hazard ratio (HR), risk ratio (RR), and 95% confidence interval (CI) were calculated to evaluate local recurrence (LR), relapse-free survival (RFS), overall survival (OS), adverse events, and cosmetic outcomes.

Results: A total of 14 articles were included in this meta-analysis. Four thousand eight hundred and sixty-nine patients were randomly assigned to the control group to receive conventional radiotherapy (CFRT); 6,072 patients were randomly assigned to the experimental group and treated with hypofractionated radiotherapy (HFRT). The results showed that there was no statistical difference between HFRT and CFRT in LR (HR = 0.99, 95%CI = 0.97-1.02,  = 0.476), RFS (HR = 0.99, 95%CI = 0.97-1.02,  = 0.485), OS (HR = 1.00, 95%CI = 0.97-1.03,  = 0.879), and cosmetic outcomes (RR = 1.03, 95%CI = 0.95-1.12,  = 0.53). In addition, HFRT showed fewer severe adverse reactions such as acute skin toxicity, induration, breast atrophy, and pain.

Conclusion: Our results suggest that there is no statistical difference between HFRT and CFRT in terms of LR, RFS, OS, and cosmetic outcomes. HFRT reduces the risk of developing toxicity reactions compared to CFRT. HFRT may be a better option for patients with early breast cancer after breast-conserving surgery.
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http://dx.doi.org/10.3389/fonc.2021.753209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8518530PMC
October 2021

Soluble Triggering Receptor Expressed on Myeloid Cells 2 From Cerebrospinal Fluid in Sleep Disorders Related to Parkinson's Disease.

Front Aging Neurosci 2021 29;13:753210. Epub 2021 Sep 29.

Department of Neurology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Triggering receptor expressed on myeloid cells 2 (TREM2) is a microglial receptor exclusively expressed in the central nervous system (CNS). It contributes to abnormal protein aggregation in neurodegenerative disorders, but its role in Parkinson's disease (PD) is still unclear. In this case-control study, we measured the concentration of the soluble fragment of TREM2 (sTREM2) in PD patients, evaluated their sleep conditions by the PD sleep scale (PDSS), and analyzed the relationship between sTREM2 and PD symptoms. We recruited 80 sporadic PD patients and 65 healthy controls without disease-related variants in TREM2. The concentration of sTREM2 in the CSF was significantly higher in PD patients than in healthy controls ( < 0.01). In the PD group, the concentration of sTREM2 had a positive correlation with α-syn in the CSF (Pearson = 0.248, = 0.027). Receiver operating characteristic curve (ROC) analyses showed that sTREM2 in the CSF had a significant diagnostic value for PD (AUC, 0.791; 95% CI, 0.711-0.871, < 0.05). The subgroup analysis showed that PD patients with sleep disorders had a significantly higher concentration of sTREM2 in their CSF ( < 0.01). The concentration of sTREM2 in the CSF had a negative correlation with the PDSS score in PD patients (Pearson = -0.555, < 0.01). The ROC analyses showed that sTREM2 in the CSF had a significant diagnostic value for sleep disorders in PD (AUC, 0.733; 95% CI, 0.619-0.846, < 0.05). Our findings suggest that CSF sTREM2 may be a potential biomarker for PD and it could help predict sleep disorders in PD patients, but multicenter prospective studies with more participants are still needed to confirm its diagnostic value in future.
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http://dx.doi.org/10.3389/fnagi.2021.753210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8511683PMC
September 2021

Improving cancer driver gene identification using multi-task learning on graph convolutional network.

Brief Bioinform 2021 Oct 13. Epub 2021 Oct 13.

Faculty of Information Engineering and Automation, Kunming University of Science and Technology, Kunming, Yunnan 650500, P. R. China.

Cancer is thought to be caused by the accumulation of driver genetic mutations. Therefore, identifying cancer driver genes plays a crucial role in understanding the molecular mechanism of cancer and developing precision therapies and biomarkers. In this work, we propose a Multi-Task learning method, called MTGCN, based on the Graph Convolutional Network to identify cancer driver genes. First, we augment gene features by introducing their features on the protein-protein interaction (PPI) network. After that, the multi-task learning framework propagates and aggregates nodes and graph features from input to next layer to learn node embedding features, simultaneously optimizing the node prediction task and the link prediction task. Finally, we use a Bayesian task weight learner to balance the two tasks automatically. The outputs of MTGCN assign each gene a probability of being a cancer driver gene. Our method and the other four existing methods are applied to predict cancer drivers for pan-cancer and some single cancer types. The experimental results show that our model shows outstanding performance compared with the state-of-the-art methods in terms of the area under the Receiver Operating Characteristic (ROC) curves and the area under the precision-recall curves. The MTGCN is freely available via https://github.com/weiba/MTGCN.
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http://dx.doi.org/10.1093/bib/bbab432DOI Listing
October 2021

Prevalence and pattern of refractive error and visual impairment among schoolchildren: the Lhasa childhood eye study.

BMC Ophthalmol 2021 Oct 12;21(1):363. Epub 2021 Oct 12.

Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Key Laboratory of Ophthalmology & Visual Sciences, No.1, Dong Jiao Min Xiang Street, Dongcheng District, Beijing, 100730, China.

Background: Early and effective ocular screening may help to eliminate treatable eye disorders. The Lhasa Childhood Eye Study (LCES) revealed the particular prevalence of refractive error and visual impairment in grade one schoolchildren (starting age of 6 years old) in Lhasa.

Methods: This is a cross-sectional part of school-based cohort study. One thousand nine hundred forty-three children were enrolled (median age, 6.78 years, range, 5.89 to 10.32). Each child underwent general and ocular examinations, including logarithm of the minimum angle of resolution (logMAR) visual acuity, cycloplegic autorefraction, and slit-lamp biomicroscopy evaluation. Multivariate and correlation analyses were performed to evaluate the association between refractive error with gender and ethnics.

Results: The prevalence of visual impairment (logMAR visual acuity ≥0.3 in the better-seeing eye) of uncorrected, presenting and best-corrected visual acuity (BCVA) was 12.2, 11.7 and 2.7%, respectively. Refractive error presented in 177 (78.0%) out of 227 children with bilateral visual impairment. Myopia (spherical equivalent refractor [SER] ≤ - 0.50 diopter [D] in either eye) was present in 4.7% children when measured after cycloplegic autorefraction. Hyperopia (SER ≥ + 2.00 D) affected 12.1% children. Hyperopia was significantly associated with female gender (P<0.001). Astigmatism (cylinder value ≤ - 0.75 D) was present in 44.8% children. In multivariate regression and correlation analysis, SER had no significant difference between ethnic groups.

Conclusion: The Lhasa Childhood Eye Study is the first school-based cohort study to reveal the prevalence and pattern of refractive error and visual impairment in Lhasa. Effective strategies such as corrective spectacles should be considered to alleviate treatable visual impairment.
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http://dx.doi.org/10.1186/s12886-021-02134-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8513166PMC
October 2021

LncRNA-SNHG1 promotes macrophage M2-like polarization and contributes to breast cancer growth and metastasis.

Aging (Albany NY) 2021 Oct 7;13(19):23169-23181. Epub 2021 Oct 7.

Department of Oncology, The People's Hospital of Rizhao, Rizhao, Shandong Province, China.

Breast cancer is one of the most common malignant cancers among women. Cancer cells and adjacent cells determine the development of the disease. Tumor associated macrophages (TAMs) are involved in the regulation of different stages of cancer progression. LncRNAs play an important role in tumor growth and metastasis. However, the function of lncRNA in macrophage and tumor cell interaction is poorly described. Here we reported that lncRNA SNHG1 functioned as a modulator of M2 macrophage polarization and regulated tumor growth and angiogenesis. We indicated that knockdown of SNHG1 inhibited M2 macrophage polarization by suppression of STAT6 phosphorylation. SNHG1 silencing significantly alleviated migration of MCF-7 cells and tube formation of Human Umbilical Vein Endothelial Cells (HUVEC). Furthermore, we found that implantation of cell mixture of MCF-7 cells and macrophages promoted tumor growth and angiogenesis. However, knockdown of SNHG1 in macrophages reversed that effect. Collectively, we demonstrated the important role of lncRNA SNHG1 in macrophages and breast cancer cells interaction. We highlight the essential effect of lncRNA in tumor progression and provide a new method for the prevention and treatment of breast tumor metastasis.
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http://dx.doi.org/10.18632/aging.203609DOI Listing
October 2021

Peritumoral B cells drive proangiogenic responses in HMGB1-enriched esophageal squamous cell carcinoma.

Angiogenesis 2021 Oct 6. Epub 2021 Oct 6.

Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, 1/F, Professorial Block, 102 Pokfulam Road, Pok Fu Lam, Hong Kong.

Several B-cell subsets with distinct functions and polarized cytokine profiles that extend beyond antibody production have been reported in different cancers. Here we have demonstrated that proliferating B cells were predominantly found in the peritumoral region of esophageal squamous cell carcinoma (ESCC). These B cells were enriched in tumor nests with high expression of high-mobility group box 1 (HMGB1). High densities of peritumoral proliferating B cells and concomitantly high intratumoral HMGB1 expression showed improved prognostic significance, surpassing prognostic stratification of ESCC patients based on HMGB1 positivity alone. This striking association led us to set up models to test whether cancer-derived HMGB1 could shape tumor microenvironment via modulation on B cells. Overexpression of HMGB1 in ESCC cell lines (KYSE510 and EC18) enhanced proliferation and migration of B cells. Transcriptomic analysis showed that migratory B cells exhibited high enrichment of proangiogenic genes. VEGF expression in proliferating B cells was induced upon co-culture of HMGB1-overexpressing tumor cells and B cells. Secretome array profiling of conditioned media (CM) from the co-culture revealed rich expression of proangiogenic proteins. Consequently, incubation of human umbilical vein endothelial cells with CM promoted angiogenesis in tube formation and migration assays. HMGB1 inhibitor, glycyrrhizin, abolishes all the observed proangiogenic phenotypes. Finally, co-injection of B cells and CM with HMGB1-overexpressing tumor cells, but not with glycyrrhizin, significantly enhanced tumor growth associated with increased microvascular density in ESCC xenograft mice model. Our results indicate that cancer-derived HMGB1 elevates angiogenesis in ESCC by shifting the balance toward proangiogenic signals in proliferating B cells.
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http://dx.doi.org/10.1007/s10456-021-09819-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8494172PMC
October 2021

Subcategorizing EHR diagnosis codes to improve clinical application of machine learning models.

Int J Med Inform 2021 Sep 21;156:104588. Epub 2021 Sep 21.

Population and Quantitative Health Sciences, School of Medicine, Case Western Reserve University, Cleveland, OH, United States.

Background: Electronic health record (EHR) data is commonly used for secondary purposes such as research and clinical decision support. However, reuse of EHR data presents several challenges including but not limited to identifying all diagnoses associated with a patient's clinical encounter. The purpose of this study was to assess the feasibility of developing a schema to identify and subclassify all structured diagnosis codes for a patient encounter.

Methods: To develop a subclassification schema we used EHR data from an interhospital transport data repository that contained complete hospital encounter level data. Eight discrete data sources containing structured diagnosis codes were identified. Diagnosis codes were normalized using the Unified Medical Language System and additional EHR data were combined with standardized terminologies to create and validate the subcategories. We then employed random forest to assess the usefulness of the new subcategorized diagnoses to predict post-interhospital transfer mortality by building 2 models, one using standard diagnosis codes, and one using the new subcategorized diagnosis codes.

Results: Six subcategories of diagnoses were identified and validated. The subcategories included: primary or admitting diagnoses (10%), past medical, surgical or social history (9%), problem list (20%), comorbidity (24%), discharge diagnoses (6%), and unmapped diagnoses (31%). The subcategorized model outperformed the standard model, achieving a training AUROC of 0.97 versus 0.95 and testing model AUROC of 0.81 versus 0.46.

Discussion: Our work demonstrates that merging structured diagnosis codes with additional EHR data and secondary data sources provides additional information to understand the role of diagnosis throughout a clinical encounter and improves predictive model performance. Further work is necessary to assess if subcategorizing produces benefits in interpreting the results of prognostic models and/or operationalizing the results in clinical decision support applications.
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http://dx.doi.org/10.1016/j.ijmedinf.2021.104588DOI Listing
September 2021

Early Patient-Reported Outcomes After Uniportal Versus Multiportal Thoracoscopic Lobectomy.

Ann Thorac Surg 2021 Sep 29. Epub 2021 Sep 29.

Department of Thoracic Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China. Electronic address:

Background: Uniportal video-assisted thoracoscopic surgery (U-VATS) can achieve comparable traditional clinical outcomes as those of multiportal video-assisted thoracoscopic surgery (M-VATS). This study aimed to compare patient-reported outcomes between U-VATS and M-VATS for lung cancer lobectomy in the early postoperative period.

Methods: This comparative analysis used data from a longitudinal prospective study (CN-PRO-Lung 1). Symptom severity, functional status, and quality of life were compared between groups using generalized estimation equation models. Symptom severity and functional status were reported as proportion of patients with clinically meaningful severe scores on 0-10-point scales assessed using the MD Anderson Symptom Inventory-Lung Cancer module.

Results: Of the 174 patients included, 102 (58.6%) underwent U-VATS lobectomy and 72 (41.4%) underwent M-VATS lobectomy. After adjusting for confounders, patients in the U-VATS group reported less severe pain (p = 0.02), fatigue (p = 0.001), constipation (p = 0.01), coughing (p = 0.003), shortness of breath (p < 0.001), and disturbed sleep (p = 0.007) during the 6-day postoperative hospitalization than those in the M-VATS group. Moreover, fewer patients reported severe impairment to walking (p = 0.033) or their capacity to enjoy life (p = 0.027) in the U-VATS group. Meanwhile, there were no significant between-group differences in the quality of life scores, operative time, chest tube duration, length of hospital stay, or early complication rate (≥ grade II) (all p ˃ 0.05).

Conclusions: U-VATS might produce fewer severe symptoms and better functional status than M-VATS for lung cancer lobectomy in the early postoperative period.
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http://dx.doi.org/10.1016/j.athoracsur.2021.08.058DOI Listing
September 2021

Suppression of lncRNA NLRP3 inhibits NLRP3-triggered inflammatory responses in early acute lung injury.

Cell Death Dis 2021 Oct 1;12(10):898. Epub 2021 Oct 1.

Department of Intensive Care Unit, The First Affiliated Hospital of Nanchang University, No. 17 Yongwaizheng Street, Dong Lake District, Nanchang, Jiangxi Province, 330000, China.

Acute lung injury (ALI) is a common lung pathology that is accompanied by alveolar macrophage (AM) activation and inflammatory response. This study investigated the role of the long non-coding RNA NONRATT004344 (hereafter named lncRNA NLRP3) in regulating the Nod-like receptor protein 3 (NLRP3)-triggered inflammatory response in early ALI and the underlying mechanism as well. We established LPS-induced ALI models to explore their interactive mechanisms in vitro and in vivo. Luciferase reporter assays were performed to determine that miR-138-5p could bind to lncRNA NLRP3 and NLRP3. We observed increased lncRNA NLRP3 expression, decreased miR-138-5p expression, NLRP3 inflammasome activation, and upregulated caspase-1, IL-1β, and IL-18 expression in the LPS-induced ALI model. Furthermore, lncRNA NLRP3 overexpression activated the NLRP3 inflammasome and promoted IL-1β and IL-18 secretion; the miR-138-5p mimic abolished these effects in vivo and in vitro. Consistently, miR-138-5p inhibition reversed the effects of lncRNA NLRP3 silencing on the expression of NLRP3-related molecules and inhibition of the NLRP3/caspase-1/IL-1β signalling pathway. Mechanistically, lncRNA NLRP3 sponging miR-138-5p facilitated NLRP3 activation through a competitive endogenous RNA (ceRNA) mechanism. In summary, our results suggested that lncRNA NLRP3 binding miR-138-5p promotes NLRP3-triggered inflammatory response via lncRNA NLRP3/miR-138-5p/NLRP3 ceRNA network (ceRNET) and provides insights into the treatment of early ALI.
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http://dx.doi.org/10.1038/s41419-021-04180-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8486756PMC
October 2021

CBX8 interacts with chromatin PTEN and is involved in regulating mitotic progression.

Cell Prolif 2021 Sep 30:e13110. Epub 2021 Sep 30.

Department of Environmental Medicine, New York University Grossman School of Medicine, New York, NY, USA.

Objectives: Besides its role in regulating phosphatidylinositol-3 kinase (PI3K) signalling in the cytosol, PTEN also has a nuclear function. In this study, we attempted to understand the mechanism of chromatin PTEN in suppressing chromosomal instability during cell division.

Materials And Methods: Immunocoprecipitation, ectopic expression, and deletional analyses were used to identify the physical interaction between Chromobox Homolog protein 8 (CBX8) and PTEN, as well as the functional domain(s) of PTEN mediating the interaction. Cell synchronization followed by immunoblotting was employed to study cell cycle regulation of CBX8 and the functional interaction between chromatin PTEN and CBX8. Small interfering RNAs (siRNAs) were used to study the role of PTEN and CBX8 in modulating histone epigenetic markers during the cell cycle.

Results: Polycomb group (PcG) proteins including CBXs function to repress gene expression in a wide range of organisms including mammals. We recently showed that PTEN interacted with CBX8, a component of Polycomb Repressing Complex 1 (PRC1), and that CBX8 co-localized with PTEN in the nucleus. CBX8 levels were high, coinciding with its phosphorylation in mitosis. Phosphorylation of CBX8 was associated with monoubiquitinated PTEN and phosphorylated-BubR1 on chromatin. Moreover, CBX8 played an important role in cell proliferation and mitotic progression. Significantly, downregulation of either PTEN or CBX8 induced H3K27Me3 epigenetic marker in mitotic cells.

Conclusion: CBX8 is a new component that physically interacts with chromatin PTEN, playing an important role in regulating mitotic progression.
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http://dx.doi.org/10.1111/cpr.13110DOI Listing
September 2021

[Continuous PM Composition Measurements for Source Apportionment During Air Pollution Events].

Huan Jing Ke Xue 2021 Oct;42(10):4575-4581

Jiangsu Key Laboratory of Atmospheric Environment Monitoring and Pollution Control, Collaborative Innovation Center of Atmospheric Environment and Equipment Technology, School of Environmental Science & Engineering, Nanjing University of Information Science & Technology, Nanjing 210044, China.

To explore the application of high-temporal-resolution data in PM source apportionment during air pollution events, ambient air PM components were continuously monitored in urban Nanjing from January to December, 2017. Commercially available instruments for continuous measurements were deployed to obtain hourly concentrations of elements, water-soluble ions, and carbonaceous components of PM. Data for 15 elements and 5 bulk components during three pollution events(firework combustion during the Spring Festival, a spring sandstorm, and a winter haze event) and across the whole year comprised four datasets for source apportionment using positive matrix factorization(PMF), and the distribution of factor/source contributions and estimations of average concentrations of characteristic components were compared based on different input datasets(PMF and PMF). The results showed that the identified factors/sources, factor profiles, and contributions differed largely between PMF and PMF solutions. For example, the relative average contribution of the firework combustion factor derived from the PMF solution(was 1.50%) was far less than that of the PMF solution. The dust factor had an average contribution of 8.51% in the PMF solution, which was approximately double that of the PMF solution. This might be explained by the fact that PMF assumes unvaried source compositions during the measurement campaign, meaning that the source apportionment results based on long-term observations will include bias due to changes in emission sources. Furthermore, during the firework combustion event, the estimated average concentration of K from the PMF solution[(1.32±1.17) μg·m, =0.64]was closer to measured value[(1.36±1.19) μg·m]than that of the PMF solution[(1.16±1.19) μg·m, =0.0090]. For the sand storm event, the concentrations of Fe, Si, and Ti were significantly underestimated by the PMF solution[(0.061±0.042)-(1.06±0.65) μg·m, <0.05], while their peak concentrations agreed well between the PMF estimations and the observations. During the winter haze event, all PM bulk components were well estimated by both the PMF and PMF solutions. Based on these results, PMF source apportionment results based on continuous measurement data during pollution events can reasonably reflect short-term variations in characteristic PM components and their sources, which can improve the timeliness of air pollution source apportionment.
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http://dx.doi.org/10.13227/j.hjkx.202102151DOI Listing
October 2021

The Stromal and Immune Landscape of Nasopharyngeal Carcinoma and Its Implications for Precision Medicine Targeting the Tumor Microenvironment.

Front Oncol 2021 10;11:744889. Epub 2021 Sep 10.

Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong, SAR China.

The evolution of the tumor microenvironment (TME) is a cancer-dependent and dynamic process. The TME is often a complex ecosystem with immunosuppressive and tumor-promoting functions. Conventional chemotherapy and radiotherapy, primarily focus on inducing tumor apoptosis and hijacking tumor growth, whereas the tumor-protective microenvironment cannot be altered or destructed. Thus, tumor cells can quickly escape from extraneous attack and develop therapeutic resistance, eventually leading to treatment failure. As an Epstein Barr virus (EBV)-associated malignancy, nasopharyngeal carcinoma (NPC) is frequently infiltrated with varied stromal cells, making its microenvironment a highly heterogeneous and suppressive harbor protecting tumor cells from drug penetration, immune attack, and facilitating tumor development. In the last decade, targeted therapy and immunotherapy have emerged as promising options to treat advanced, metastatic, recurrent, and resistant NPC, but lack of understanding of the TME had hindered the therapeutic development and optimization. Single-cell sequencing of NPC-infiltrating cells has recently deciphered stromal composition and functional dynamics in the TME and non-malignant counterpart. In this review, we aim to depict the stromal landscape of NPC in detail based on recent advances, and propose various microenvironment-based approaches for precision therapy.
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http://dx.doi.org/10.3389/fonc.2021.744889DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8462296PMC
September 2021

Activity-based RNA-modifying enzyme probing reveals DUS3L-mediated dihydrouridylation.

Nat Chem Biol 2021 Sep 23. Epub 2021 Sep 23.

Department of Chemistry, Princeton University, Princeton, NJ, USA.

Epitranscriptomic RNA modifications can regulate RNA activity; however, there remains a major gap in our understanding of the RNA chemistry present in biological systems. Here we develop RNA-mediated activity-based protein profiling (RNABPP), a chemoproteomic strategy that relies on metabolic RNA labeling, mRNA interactome capture and quantitative proteomics, to investigate RNA-modifying enzymes in human cells. RNABPP with 5-fluoropyrimidines allowed us to profile 5-methylcytidine (mC) and 5-methyluridine (mU) methyltransferases. Further, we uncover a new mechanism-based crosslink between 5-fluorouridine (5-FUrd)-modified RNA and the dihydrouridine synthase (DUS) homolog DUS3L. We investigate the mechanism of crosslinking and use quantitative nucleoside liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis and 5-FUrd-based crosslinking and immunoprecipitation (CLIP) sequencing to map DUS3L-dependent dihydrouridine (DHU) modifications across the transcriptome. Finally, we show that DUS3L-knockout (KO) cells have compromised protein translation rates and impaired cellular proliferation. Taken together, our work provides a general approach for profiling RNA-modifying enzyme activity in living cells and reveals new pathways for epitranscriptomic RNA regulation.
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http://dx.doi.org/10.1038/s41589-021-00874-8DOI Listing
September 2021

PncsHub: a platform for annotating and analyzing non-classically secreted proteins in Gram-positive bacteria.

Nucleic Acids Res 2021 Sep 22. Epub 2021 Sep 22.

Infection and Immunity Program, Biomedicine Discovery Institute and Department of Microbiology, Monash University, VIC 3800, Australia.

From industry to food to health, bacteria play an important role in all facets of life. Some of the most important bacteria have been purposely engineered to produce commercial quantities of antibiotics and therapeutics, and non-classical secretion systems are at the forefront of these technologies. Unlike the classical Sec or Tat pathways, non-classically secreted proteins share few common characteristics and use much more diverse secretion pathways for protein transport. Systematically categorizing and investigating the non-classically secreted proteins will enable a deeper understanding of their associated secretion mechanisms and provide a landscape of the Gram-positive secretion pathway distribution. We therefore developed PncsHub (https://pncshub.erc.monash.edu/), the first universal platform for comprehensively annotating and analyzing Gram-positive bacterial non-classically secreted proteins. PncsHub catalogs 4,914 non-classically secreted proteins, which are delicately categorized into 8 subtypes (including the 'unknown' subtype) and annotated with data compiled from up to 26 resources and visualisation tools. It incorporates state-of-the-art predictors to identify new and homologous non-classically secreted proteins and includes three analytical modules to visualise the relationships between known and putative non-classically secreted proteins. As such, PncsHub aims to provide integrated services for investigating, predicting and identifying non-classically secreted proteins to promote hypothesis-driven laboratory-based experiments.
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http://dx.doi.org/10.1093/nar/gkab814DOI Listing
September 2021

Recent developments in mussel-inspired materials for biomedical applications.

Biomater Sci 2021 Oct 12;9(20):6653-6672. Epub 2021 Oct 12.

Terasaki Institute for Biomedical Innovation, Los Angeles, CA 90024, USA.

Over the decades, researchers have strived to synthesize and modify nature-inspired biomaterials, with the primary aim to address the challenges of designing functional biomaterials for regenerative medicine and tissue engineering. Among these challenges, biocompatibility and cellular interactions have been extensively investigated. Some of the most desirable characteristics for biomaterials in these applications are the loading of bioactive molecules, strong adhesion to moist areas, improvement of cellular adhesion, and self-healing properties. Mussel-inspired biomaterials have received growing interest mainly due to the changes in mechanical and biological functions of the scaffold due to catechol modification. Here, we summarize the chemical and biological principles and the latest advancements in production, as well as the use of mussel-inspired biomaterials. Our main focus is the polydopamine coating, the conjugation of catechol with other polymers, and the biomedical applications that polydopamine moieties are used for, such as matrices for drug delivery, tissue regeneration, and hemostatic control. We also present a critical conclusion and an inspired view on the prospects for the development and application of mussel-inspired materials.
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http://dx.doi.org/10.1039/d1bm01126jDOI Listing
October 2021

Enhanced functional connectivity between habenula and salience network in medication-overuse headache complicating chronic migraine positions it within the addiction disorders: an ICA-based resting-state fMRI study.

J Headache Pain 2021 Sep 9;22(1):107. Epub 2021 Sep 9.

Department of Neurology, Chinese PLA General Hospital, 28 Fuxing Road, 100853, Beijing, China.

Background: Medication-overuse headache (MOH) is a relatively frequently occurring secondary headache caused by overuse of analgesics and/or acute migraine medications. It is believed that MOH is associated with dependence behaviors and substance addiction, in which the salience network (SN) and the habenula may play an important role. This study aims to investigate the resting-state (RS) functional connectivity between the habenula and the SN in patients with MOH complicating chronic migraine (CM) compared with those with episodic migraine (EM) and healthy controls (HC).

Methods: RS-fMRI and 3-dimensional T1-weighted images of 17 patients with MOH + CM, 18 patients with EM and 30 matched healthy HC were obtained. The RS-fMRI data were analyzed using the independent component analysis (ICA) method to investigate the group differences of functional connectivity between the habenula and the SN in three groups. Correlation analysis was performed thereafter with all clinical variables by Pearson correlation.

Results: Increased functional connectivity between bilateral habenula and SN was detected in patients with MOH + CM compared with patients with EM and HC respectively. Correlation analysis showed significant correlation between medication overuse duration and habenula-SN connectivity in MOH + CM patients.

Conclusions: The current study supported MOH to be lying within a spectrum of dependence and addiction disorder. The enhanced functional connectivity of the habenula with SN may correlate to the development or chronification of MOH. Furthermore, the habenula may be an indicator or treatment target for MOH for its integrative role involved in multiple aspects of MOH.
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http://dx.doi.org/10.1186/s10194-021-01318-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8428097PMC
September 2021

Stereoacuity and its determinants in 7-year-old children: the Lhasa Childhood Eye Study.

Graefes Arch Clin Exp Ophthalmol 2021 Sep 9. Epub 2021 Sep 9.

Department of Strabismus and Pediatric Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, No. 1 Dongjiaominxiang Street, Dongcheng District, 100730, Beijing, China.

Purpose: To explore the distribution of stereoacuity and to examine its determinants in school-age children in Tibetan plateau, Southwest China.

Methods: This is the cross-sectional part of a school-based cohort study of 7-year-old children in Lhasa, Tibet Autonomous Region, Southwest China. Children in first year of primary school were invited to undergo a comprehensive examination, including height, weight, visual acuity, cycloplegic autorefraction (1% cyclopentolate), anterior segment, cover and uncover test, and stereoacuity (Titmus Stereo Test).

Results: A total of 1833 eligible subjects were included, with a mean age of 6.82 ± 0.46 years. Mean stereoacuity was 1.78 ± 0.21 in log units (median: 60 arcsec). Children with stereoacuity equal to 40 arcsec and stereoacuity worse than 100 arcsec accounted for 29.24% and 8.18% of the cohort, respectively. Tibetan ethnicity (OR = 1.98; 95%CI, 1.30-3.03), astigmatism (OR = 1.65; 95%CI, 1.26-2.17), strabismus (OR = 2.92; 95%CI, 1.38-6.18), and amblyopia (OR = 3.77; 95%CI, 1.14-12.49) were risk factors for normal stereoacuity (= 40 arcsec). Shorter height, younger age, strabismus, and worse BCVA (P < 0.05 for all) were both related to lower stereoacuity in Spearman correlation analysis and associated with lower stereoacuity in multivariate regression analysis.

Conclusion: Stereoacuity maturation does not appear fully completed in 7-year-old children, while few children present stereoacuity worse than 100 arcsec (8.18%). Lower stereoacuity was associated with younger age, shorter height, strabismus, and lower best-corrected visual acuity.
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http://dx.doi.org/10.1007/s00417-021-05390-yDOI Listing
September 2021

Combination of Manifold Learning and Deep Learning Algorithms for Mid-Term Electrical Load Forecasting.

IEEE Trans Neural Netw Learn Syst 2021 Sep 3;PP. Epub 2021 Sep 3.

Mid-term load forecasting (MTLF) is of great significance for power system planning, operation, and power trading. However, the mid-term electrical load is affected by the coupling of multiple factors and demonstrates complex characteristics, which leads to low prediction accuracy in MTLF. Furthermore, MTLF is faced with the ``curse of dimensionality'' problem due to a large number of variables. This article proposes an MTLF method based on manifold learning, which can extract the underlying factors of load variations to help improve the accuracy of MTLF and significantly reduce the calculation. Unlike linear dimensionality reduction methods, manifold learning has better nonlinear feature extraction ability and is more suitable for load data with nonlinear characteristics. Furthermore, long short-term memory (LSTM) neural networks are used to establish forecasting models in the low-dimensional space obtained by manifold learning. The proposed MTLF method is tested on independent system operator (ISO) New England datasets, and load forecasting in 24, 168, and 720 h ahead is carried out. The numerical results validate that the proposed method has higher prediction accuracy than many mature methods in the mid-term time scale.
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http://dx.doi.org/10.1109/TNNLS.2021.3106968DOI Listing
September 2021

Discrepancy in the perception of symptoms among patients and healthcare providers after lung cancer surgery.

Support Care Cancer 2021 Aug 27. Epub 2021 Aug 27.

Center for Cancer Prevention Research, School of Medicine, Sichuan Cancer Hospital, University of Electronic Science and Technology of China, No. 55, Section 4, South Renmin Road, Chengdu, 610041, China.

Purpose: Patients who undergo surgery for lung cancer experience a variety of symptoms, such as pain and coughing, which interfere with their postoperative daily functions. However, there may be differences between the perception of symptoms among healthcare providers and patients. This study aimed to investigate patients' experiences after lung cancer surgery and analyze whether the perception of postoperative symptoms among the healthcare providers differed from that reported by patients.

Methods: Semi-structured qualitative interviews involving 39 patients who underwent lung cancer surgery at the Sichuan Cancer Hospital were conducted between November 2018 and October 2019. In addition, 22 healthcare providers from the Department of Thoracic Surgery at the hospital answered open-ended questions about their perception of symptoms related to lung cancer surgery. The types and frequencies of symptoms reported by the patients and healthcare providers were compared.

Results: The most frequent patient-reported symptoms were pain (967 times, 39 patients, 100%), coughing (904 times, 37 patients, 94.87%), shortness of breath (491 times, 35 patients, 89.74%), Disturbed sleep (412 times, 34 patients, 87.18%), and interference while walking (347 times, 36 patients, 92.31%). Of the patient-reported symptoms, the first four were perceived by the healthcare providers, while they interpreted interference while walking as fatigue.

Conclusion: Although the healthcare providers and patients had a certain consensus on the main symptoms, there were differences in perception. Healthcare providers need to pay more attention to postoperative interference while walking.
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http://dx.doi.org/10.1007/s00520-021-06506-0DOI Listing
August 2021

Effect of Polystyrene Microplastics on Rice Seed Germination and Antioxidant Enzyme Activity.

Toxics 2021 Jul 30;9(8). Epub 2021 Jul 30.

College of Forestry, Beijing Forestry University, Beijing 100083, China.

The accumulation and distribution of microplastics (MPs) in agricultural soils, including rice fields, is well studied. However, only a few studies have investigated the uptake of MPs by rice plants and the consequential toxic effects of MPs under solid-phase culture conditions. Hence, in this study, we explored the effects of different concentrations of polystyrene MPs (PS-MPs, with a size of 200 nm) on rice seed germination, root growth, antioxidant enzyme activity, and transcriptome. PS-MPs exhibited no significant effect on the germination of rice seeds ( > 0.05). However, PS-MPs significantly promoted root length (10 mg L; < 0.05), and significantly reduced antioxidant enzyme activity (1000 mg L; < 0.05). Staining with 3,3-diaminobenzidine and nitrotetrazolium blue chloride further revealed significant accumulation of reactive oxygen species in the roots of rice treated with PS-MPs. In addition, transcriptome data analysis revealed that PS-MPs induce the expression of genes related to antioxidant enzyme activity in plant roots. Specifically, genes related to flavonoid and flavonol biosynthesis were upregulated, whereas those involved in linolenic acid and nitrogen metabolism were downregulated. These results enhance our understanding of the responses of agricultural crops to MP toxicity.
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http://dx.doi.org/10.3390/toxics9080179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402430PMC
July 2021

Azithromycin induces apoptosis in airway smooth muscle cells through mitochondrial pathway in a rat asthma model.

Ann Transl Med 2021 Jul;9(14):1181

Department of Pulmonary Medicine, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Background: The proliferation of airway smooth muscle cells (ASMCs) is a key feature of airway remodeling in asthma. Azithromycin (AZM) has been shown to decrease bronchial hyperresponsiveness and airway inflammation in asthmatics; however, the role of AZM in ASMC proliferation remains unclear. Thus, we investigated the effect of AZM on ASMC proliferation in a rat model of experimental asthma.

Methods: We isolated ASMCs from rats sensitized and challenged by ovabulmin (OVA), and then treated with different concentrations of AZM. Cytotoxicity of ASMC was evaluated by Cell Counting Kit-8 (CCK-8) assay, morphological change was examined with laser confocal microscope after Annexin V/propidium iodide (PI) double staining, mitochondrial membrane potential was determined with JC-1 staining, and the expression of cytochrome C was examined by western blot.

Results: The relative surface areas of airway wall and smooth muscle layers in OVA-sensitized rats were significantly increased compared to those in the control group. Furthermore, in OVA-sensitized rats, the mitochondrial membrane potential of ASMC was higher, while the expression of mitochondria cytochrome C was lower compared to that in control rats. After AZM treatment, ASMC apoptosis was increased, mitochondrial membrane potential reduced, and the protein level of cytosolic cytochrome C was increased.

Conclusions: This study demonstrated that AZM increased the apoptosis of ASMCs through a mitochondrial pathway, which might play an important role in ASMs proliferation during asthmatic remodeling.
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http://dx.doi.org/10.21037/atm-21-3478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350718PMC
July 2021

Retraction Note to: Lupeol enhances inhibitory effect of 5-fluorouracil on human gastric carcinoma cells.

Naunyn Schmiedebergs Arch Pharmacol 2021 Oct;394(10):2145

Department of General Surgery, Wujiang No. 1 People's Hospital, Suzhou, 215200, China.

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http://dx.doi.org/10.1007/s00210-021-02141-yDOI Listing
October 2021

All-Solid-State Thin Film μ-Batteries for Microelectronics.

Adv Sci (Weinh) 2021 Oct 5;8(19):e2100774. Epub 2021 Aug 5.

Department of Mechanical Engineering, National University of Singapore, Singapore, 117575, Singapore.

Continuous advances in microelectronics and micro/nanoelectromechanical systems enable the use of microsized energy storage devices, namely solid-state thin-film μ-batteries. Different from the current button batteries, the μ-battery can directly be integrated on microchips forming a very compact "system on chip" since no liquid electrolyte is used in the μ-battery. The all-solid-state battery (ASSB) that uses solid-state electrolyte has become a research trend because of its high safety and increased capacity. The solid-state thin-film μ-battery belongs to the family of ASSB but in a small format. However, a lot of scientific and technical issues and challenges are to be resolved before its real application, including the ionic conductivity of the solid-state electrolyte, the electrical conductivity of the electrode, integration technologies, electrochemical-induced strain, etc. To achieve this goal, understanding the processing of thin films and fundamentals of ion transfer in the solid-state electrolytes and hence in the μ-batteries becomes utmost important. This review therefore focuses on solid-state ionics and provides inside of ion transportation in the solid state and effects of chemistry on electrochemical behaviors and proposes key technology for processing of the μ-battery.
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http://dx.doi.org/10.1002/advs.202100774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8498886PMC
October 2021

Predicting Drug Response Based on Multi-omics Fusion and Graph Convolution.

IEEE J Biomed Health Inform 2021 Aug 4;PP. Epub 2021 Aug 4.

Different cancer patients may respond differently to cancer treatment due to the heterogeneity of cancer. It is an urgent task to develop an efficient computational method to identify drug responses in different cell lines, which guides us to design personalized therapy for an individual patient. Hence, we propose an end-to-end algorithm, namely MOFGCN, to predict drug response in cell lines based on Multi-Omics Fusion and Graph Convolution Network. MOFGCN first fuses multiple omics data to calculate the cell line similarity and then constructs a heterogeneous network by combining the cell line similarity, drug similarity, and the known cell line-drug associations. Secondly, it learns the latent features for cancer cell lines and drugs by performing graph convolution operations on the heterogeneous network. Finally, MOFGCN applies the linear correlation coefficient to reconstruct the cancer cell line-drug correlation matrix to predict drug sensitivity. To our knowledge, this is the first attempt to combine graph convolutional neural network and linear correlation coefficient for this significant task. We performed extensive evaluation experiments on the Genomics of Drug Sensitivity in Cancer (GDSC) and Cancer Cell Line Encyclopedia (CCLE) databases to validate MOFGCNs performance. The experimental results show that MOFGCN is superior to the state-of-the-art algorithms in predicting missing drug responses. It also leads to higher performance in predicting drug responses for new cell lines, new drugs, and targeted drugs.
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http://dx.doi.org/10.1109/JBHI.2021.3102186DOI Listing
August 2021

Genetic variants of CYP4F12 gene are associated with glioma susceptibility.

Int J Cancer 2021 Dec 28;149(11):1910-1915. Epub 2021 Aug 28.

Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.

Glioma is a common and fatal primary malignant tumor of the central nervous system, and its prognosis is poor. To determine the susceptibility markers of gliomas in Chinese population we conducted a genome-wide association study (GWAS) of glioma in the Han Chinese population, with a total of 485 glioma cases and 485 controls. Genotyping was conducted using the Applied Biosystems Axiom Precision Medicine Diversity Array. Besides, we carried out imputation using IMPUTE 2.0 software, and the 1000 Genomes Phase 3 was used as the reference panel. The logistic regression model was used to analyze the association of each SNP with glioma risk, assuming an additive genetic model, which was implemented in PLINK version 1.9. Odds ratio (OR) and 95% confidence interval (CI) were estimated from logistic regression analysis with adjustment for age and gender. The results revealed that the SNP (rs688755) in the exon region of CYP4F12 at 19p13.12 reached genome-wide significance associated with gliomas (P = 2.35 × 10 , OR = 3.55, 95% CI = 2.20-5.74). Our findings provide deeper insight into the genetic contribution to glioma in different populations.
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http://dx.doi.org/10.1002/ijc.33755DOI Listing
December 2021
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