A two-stage genome-wide association study identifies novel germline genetic variations in CACNA2D3 associated with radiotherapy response in nasopharyngeal carcinoma.

BACKGROUND: Radiotherapy (RT) is the standard treatment for nasopharyngeal carcinoma (NPC). However, due to individual differences in radiosensitivity, biomarkers are needed to tailored radiotherapy to cancer patients. However, comprehensive genome-wide radiogenomic studies on them are still lacking. The aim of this study was to identify genetic variants associated with radiotherapy response in patients with NPC. METHODS: This was a large­scale genome-wide association analysis (GWAS) including a total of 981 patients. 319 individuals in the discovery stage were genotyped for 688,783 SNPs using whole genome-wide screening microarray. Significant loci were further genotyped using MassARRAY system and TaqMan SNP assays in the validation stages of 847 patients. This study used logistic regression analysis and multiple bioinformatics tools such as PLINK, LocusZoom, LDBlockShow, GTEx, Pancan-meQTL and FUMA to examine genetic variants associated with radiotherapy efficacy in NPC. RESULTS: After genome-wide level analysis, 19 SNPs entered the validation stage (P < 1 × 10- 6), and rs11130424 ultimately showed statistical significance among these SNPs. The efficacy was better in minor allele carriers of rs11130424 than in major allele carriers. Further stratified analysis showed that the association existed in patients in the EBV-positive, smoking, and late-stage (III and IV) subgroups and in patients who underwent both concurrent chemoradiotherapy and induction/adjuvant chemotherapy. CONCLUSION: Our study showed that rs11130424 in the CACNA2D3 gene was associated with sensitivity to radiotherapy in NPC patients. TRIAL REGISTRATION NUMBER: Effect of genetic polymorphism on nasopharyngeal carcinoma chemoradiotherapy reaction, ChiCTR-OPC-14005257, Registered 18 September 2014, http://www.chictr.org.cn/showproj.aspx?proj=9546 .

Evolution of the DEHYDRATION-RESPONSIVE ELEMENT-BINDING PROTEIN subfamily in green plants.

Adapting to unfavorable environments is a necessary step in plant terrestrialization and radiation. The dehydration-responsive element-binding (DREB) protein subfamily plays a pivotal role in plant abiotic stress regulation. However, relationships between the origin and expansion of the DREB subfamily and adaptive evolution of land plants are still being elucidated. Here, we constructed the evolutionary history of the DREB subfamily by compiling APETALA2/ethylene-responsive element-binding protein superfamily genes from 169 representative species of green plants. Through extensive phylogenetic analyses and comparative genomic analysis, our results revealed that the DREB subfamily diverged from the ethylene-responsive factor (ERF) subfamily in the common ancestor of Zygnemophyceae and Embryophyta during the colonization of land by plants, followed by expansions to form three different ancient archetypal genes in Zygnemophyceae species, designated as groups archetype-I, archetype-II/III, and archetype-IV. Four large-scale expansions paralleling the evolution of land plants led to the nine-subgroup divergence of group archetype-II/III in angiosperms, and five whole-genome duplications during Brassicaceae and Poaceae radiation shaped the diversity of subgroup IIb-1. We identified a Poaceae-specific gene in subgroup IIb-1, ERF014, remaining in a Poaceae-specific microsynteny block and co-evolving with a small heat shock protein cluster. Expression analyses demonstrated that heat acclimation may have driven the neofunctionalization of ERF014s in Pooideae by engaging in the conserved heat-responsive module in Poaceae. This study provides insights into lineage-specific expansion and neofunctionalization in the DREB subfamily, together with evolutionary information valuable for future functional studies of plant stress biology.

A two-stage genome-wide association study to identify novel genetic loci associated with acute radiotherapy toxicity in nasopharyngeal carcinoma.

BACKGROUND: Genetic variants associated with acute side effects of radiotherapy in nasopharyngeal carcinoma (NPC) remain largely unknown. METHODS: We performed a two-stage genome-wide association analysis including a total of 1084 patients, where 319 individuals in the discovery stage were genotyped for 688,783 SNPs using whole genome-wide screening microarray. Significant variants were then validated in an independent cohort of 765 patients using the MassARRAY system. Gene mapping, linkage disequilibrium, genome-wide association analysis, and polygenic risk score were conducted or calculated using FUMA, LDBlockShow, PLINK, and PRSice software programs, respectively. RESULTS: Five SNPs (rs6711678, rs4848597, rs4848598, rs2091255, and rs584547) showed statistical significance after validation. Radiotherapy toxicity was more serious in mutant minor allele carriers of all five SNPs. Stratified analysis further indicated that rs6711678, rs4848597, rs4848598, and rs2091255 correlated with skin toxicity in patients of EBV positive, late stage (III and IV), receiving both concurrent chemoradiotherapy and induction/adjuvant chemotherapy, and with OR values ranging from 1.92 to 2.66. For rs584547, high occurrence of dysphagia was found in A allele carriers in both the discovery (P = 1.27 × 10- 6, OR = 1.55) and validation (P = 0.002, OR = 4.20) cohorts. Furthermore, prediction models integrating both genetic and clinical factors for skin reaction and dysphagia were established. The area under curve (AUC) value of receiver operating characteristic (ROC) curves were 0.657 (skin reaction) and 0.788 (dysphagia). CONCLUSIONS: Rs6711678, rs4848597, rs4848598, and rs2091255 on chromosome 2q14.2 and rs584547 were found to be novel risk loci for skin toxicity and dysphagia in NPC patients receiving radiotherapy. TRIAL REGISTRATION: Chinese Clinical Trial Register (registration number: ChiCTR-OPC-14005257 and CTXY-140007-2).

Whole-body hyperthermia combined with chemotherapy and intensity-modulated radiotherapy for treatment of advanced nasopharyngeal carcinoma: a retrospective study with propensity score matching.

BACKGROUND: Several studies have reported the combination of intracavity or cervical lymph node hyperthermia with chemoradiotherapy (CRT) to improve clinical outcomes in nasopharyngeal carcinoma (NPC), but the combination with whole-body hyperthermia (WBH) for treating NPC is unexplored. We aimed to assess the efficacy of the combination of radiotherapy, chemotherapy and WBH in patients with locoregionally advanced NPC. METHODS: Between July 2008 and November 2012, 239 newly diagnosed NPC patients were enrolled in a pre-propensity score-matched cohort, including 193 patients who received CRT (CRT group) and 46 who underwent CRT with WBH (HCRT group). The feasibility and clinical outcomes of both groups were evaluated and toxicities assessed. Survival rates were assessed using the Kaplan-Meier method, log-rank test and Cox regression. RESULTS: Following propensity score matching, 46 patients from each group were included. The 5-year overall survival (OS) rates were 65.2% in the CRT group and 80.3% in the HCRT group (p=.027). In contrast, the other survival outcomes at 5 years were similar between the groups: locoregional recurrence-free survival (LRRFS), 74.7% vs. 87.6% (p=.152); distant metastasis-free survival (DMFS), 67.4% vs. 77.9% (p=.125); and progression-free survival (PFS), 53.1% vs. 69.2% (p=.115). In the multivariate analyses, the only two independent predictors of OS were clinical stage and HCRT. CONCLUSIONS: These results suggest that WBH, when combined with CRT, can improve the OS of patients with advanced NPC.

Real-Time Imaging Redox Status in Biothiols and Ferric Metabolism of Cancer Cells in Ferroptosis Based on Switched Fluorescence Response of Gold Carbon Dots.

Ferroptosis is an iron-dependent form of regulated cell death. In this study, a ratiometric fluorescent probe, gold carbon dots (GCDs) consisting of carbon skeleton and gold nanoclusters, was used for in situ imaging to monitor redox status in biothiols (glutathione and cysteine) and ferric metabolism of cancer cells in ferroptosis. The as-prepared GCDs can selectively respond to biothiols, interestingly, the fluorescence may be switched to sense ferric ions without interference by biothiols under proper conditions. The robust GCDs-probe exhibits excellent photobleaching resistance and can reversibly respond to intracellular biothiols/ferric ion with high temporal resolution. The 8 h real-time imaging of living cells was employed to track the fluctuation of biothiols, showing the change of redox status in ferroptosis. In addition, release of ferric ions in cells was monitored. The real-time imaging of depletion of biothiols and release of ferric ion in cells indicates the GCDs-probe can monitor how the ferroptosis regulates redox status in biothiols and ferric metabolism.

Genetic and phenotypic frequency distribution of CYP2C9, CYP2C19 and CYP2D6 in over 3200 Han Chinese.

PURPOSE: This retrospective study analyzed the polymorphisms and phenotypic frequencies of CYP2C9, CYP2C19 and CYP2D6 in a Han Chinese population. METHODS: Tests for polymorphisms of CYP2C9, CYP2C19 and CYP2D6 were performed in over 3000 (3099-3931) samples using an Illumina HiSeq X Ten sequencer. Following the guidance of the PharmGKB and PharmVar databases, the polymorphisms of CYP2C9, CYP2C19 and CYP2D6 were transformed into phenotypes, which included ultrarapid metabolizers (UMs), rapid metabolizers (RMs), normal metabolizers (NMs), intermediate metabolizers (IMs) and poor metabolizers (PMs). RESULTS: A total of 3122 samples were tested for polymorphisms in CYP2C9 and the overall polymorphism frequency was found to be 8.8%; the phenotypic frequency for CYP2C9 was 91.2% NMs, 8.23% IMs and 0.16%, PMs. The overall polymorphism frequency of CYP2C19 was tested in 3099 samples and found to be 60.1%; the phenotypic frequency for CYP2C19 was 39.9% NMs, with 1.06% RMs, 45.62% IMs and 13.42% PMs. The overall polymorphism frequency of CYP2D6 was tested in 3931 samples and found to be 88.04%; the phenotypic frequency of CYP2D6 was 95.43% NMs, 3.35% IMs and 0.52% PMs. Using 2690 samples, the polymorphisms and phenotypic distributions of CYP2C9, CYP2C19 and CYP2D6 were examined simultaneously. We found that 96.36% of the samples contained mutations while 66.51% corresponded with phenotypic changes. CONCLUSIONS: Polymorphisms and phenotypic changes of CYP2C9, CYP2C19 and CYP2D6 are relatively frequent in the Han Chinese population. Thus, preemptive pharmacogenetic testing of CYP2C9, CYP2C19 and CYP2D6 should be recommended prior to dosing substrate drugs.

Effects of Cold Jet Atmospheric Pressure Plasma on the Structural Characteristics and Immunoreactivity of Celiac-Toxic Peptides and Wheat Storage Proteins.

The present research reported the effects of structural properties and immunoreactivity of celiac-toxic peptides and wheat storage proteins modified by cold jet atmospheric pressure (CJAP) plasma. It could generate numerous high-energy excited atoms, photons, electrons, and reactive oxygen and nitrogen species, including O3, H2O2, •OH, NO2- and NO3- etc., to modify two model peptides and wheat storage proteins. The Orbitrap HR-LC-MS/MS was utilized to identify and quantify CJAP plasma-modified model peptide products. Backbone cleavage of QQPFP and PQPQLPY at specific proline and glutamine residues, accompanied by hydroxylation at the aromatic ring of phenylalanine and tyrosine residues, contributed to the reduction and modification of celiac-toxic peptides. Apart from fragmentation, oxidation, and agglomeration states were evaluated, including carbonyl formation and the decline of γ-gliadin. The immunoreactivity of gliadin extract declined over time, demonstrating a significant decrease by 51.95% after 60 min of CJAP plasma treatment in vitro. The CJAP plasma could initiate depolymerization of gluten polymer, thereby reducing the amounts of large-sized polymers. In conclusion, CJAP plasma could be employed as a potential technique in the modification and reduction of celiac-toxic peptides and wheat storage proteins.

Radiomics features of ascending and descending nasopharyngeal carcinoma. / ä¸Šè¡Œåž‹ä¸Žä¸‹è¡Œåž‹é¼»å’½ç™Œç›¸å ³å½±åƒç»„å­¦ç‰¹å¾.

OBJECTIVES: To evaluate the application value of CT-based radiomics features for the ascending and descending types of nasopharyngeal carcinoma (NPC). METHODS: A total of 217 NPC patients (48 ascending type and 169 descending type), who obtained CT images before radiotherapy in Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University from February 2015 to October 2017, were analyzed retrospectively. All patients were randomly divided into a training set (n=153) and a test set (n=64). Gross tumor volume in the nasopharynx (GTVnx) was selected as regions of interest (ROI) and was analyzed by radiomics. A total of 1 300 radiomics features were extracted via IBEX. The least absolute shrinkage and selection operator (LASSO) logistic regression was performed to choose the significant features. Support vector machine (SVM) and random forest (RF) classifiers were built and verified. RESULTS: Six features were selected by the LASSO from 1 300 radiomics features. Compared with SVM classifier, RF classifier showed better classification performance. The area under curve (AUC) of the receiver operating characteristic (ROC) curve, accuracy, sensitivity, and specificity were 0.989, 0.941, 1.000, and 0.924, respectively for the training set; 0.994, 0.937, 1.000, and 0.924, respectively for the validation set. CONCLUSIONS: CT-based radiomics features possess great potential in differentiating ascending and descending NPC. It provides a certain basis for accurate medical treatment of NPC, and may affect the treatment strategy of NPC in the future.

NIR-Light-Triggered Anticancer Strategy for Dual-Modality Imaging-Guided Combination Therapy via a Bioinspired Hybrid PLGA Nanoplatform.

A promising approach toward cancer therapy is expected to integrate imaging and therapeutic agents into a versatile nanocarrier for achieving improved antitumor efficacy and reducing the side effects of conventional chemotherapy. Herein, we designed a poly(d,l-lactic- co-glycolic acid) (PLGA)-based theranostic nanoplatform using the double emulsion solvent evaporation method (W/O/W), which is associated with bovine serum albumin (BSA) modifications, to codeliver indocyanine green (ICG), a widely used near-infrared (NIR) dye, and doxorubicin (Dox), a chemotherapeutic drug, for dual-modality imaging-guided chemo-photothermal combination cancer therapy. The resultant ICG/Dox co-loaded hybrid PLGA nanoparticles (denoted as IDPNs) had a diameter of around 200 nm and exhibited excellent monodispersity, fluorescence/size stability, and biocompatibility. It was confirmed that IDPNs displayed a photothermal effect and that the heat induced faster release of Dox, which led to enhanced drug accumulation in cells and was followed by their efficient escape from the lysosomes into the cytoplasm and drug diffusion into the nucleus, resulting in a chemo-photothermal combinatorial therapeutic effect in vitro. Moreover, the IDPNs exhibited a high ability to accumulate in tumor tissue, owing to the enhanced permeability and retention (EPR) effect, and could realize real-time fluorescence/photoacoustic imaging of solid tumors with a high spatial resolution. In addition, the exposure of tumor regions to NIR irradiation could enhance the tumor penetration ability of IDPNs, almost eradicating subcutaneous tumors. In addition, the inhibition rate of IDPNs used in combination with laser irradiation against EMT-6 tumors in tumor-bearing nude mice (chemo-photothermal therapy) was approximately 95.6%, which was much higher than that for chemo- or photothermal treatment alone. Our study validated the fact that the use of well-defined IDPNs with NIR laser treatment could be a promising strategy for the early diagnosis and passive tumor-targeted chemo-photothermal therapy for cancer.

Pharmacogenomics guidelines: Current status and future development.

Genetic polymorphisms impact biological responses to drugs. Current pharmacogenomics guidelines formulated by different countries, such as the Clinical Pharmacogenetics Implementation Consortium, the Dutch Pharmacogenetics Working Group, the Canadian Pharmacogenomics Network for Drug Safety, and the French National Network (Réseau) of Pharmacogenetics, play important roles in clinical practices. However, the standards for these guidelines vary significantly, resulting in differences in recommendations. The present article discusses these differences by head-to-head comparison of the existing pharmacogenomics guidelines and proposes new strategies for their future development.

AdipoRon prevents l-thyroxine or isoproterenol-induced cardiac hypertrophy through regulating the AMPK-related pathway.

Cardiac hypertrophy is a risk factor which can intrigue heart failure. In the present study, we explored whether AdipoRon attenuates isoprenaline (ISO) or l-thyroxine-induced cardiac hypertrophy in Sprague-Dawley (SD) rats and whether the anti-hypertrophy effect is mediated by AMPK-related pathway. Here, cardiac hypertrophy was induced by injection of l-thyroxine or ISO in SD rats. In the treatment group, AdipoRon was co-administered. We examined the effects of AdipoRon on cardiac hypertrophy and hypertrophy signaling pathway. The weight of SD rats was recorded every day. Rats were killed for collection of blood and heart under anesthesia. The left heart weight and heart weight were weighed. Paraffin-embedded heart tissue regions (4 µm) were stained with hematoxylin and eosin or Masson to detect left heart hypertrophy and myocardial fibrosis. The serum BNP levels were determined by using an enzyme-linked immunosorbent assay. The mRNA levels of ANP, BNP, PGC-1α, and ERRα were evaluated by real-time PCR analysis. The protein expression levels of PGC-1α, ERRα, and pAMPK/AMPK were determined by western blot analysis. The results showed that AdipoRon significantly reversed heart weight (HW)/body weight (BW) ratio, left ventricular (LV)/BW ratio, serum BNP level and the mRNA level of ANP and BNP induced by ISO or l-thyroxine. ISO or l-thyroxine reduced both the mRNA level and protein level of ERRα and PGC-1α, and also reduced the protein level of pAMPK/AMPK. However, AdipoRon reversed ISO or l-thyroxine-induced changes of pAMPK/AMPK, ERRα, and PGC-1α. Our data indicated that the effects of AdipoRon are mediated partly by activating AMPK-related pathway, and AdipoRon plays a potential role in the prevention of cardiac hypertrophy.

Prompting peroxidase-like activity of gold nanorod composites by localized surface plasmon resonance for fast colorimetric detection of prostate specific antigen.

The interaction between incident light and surface electrons in conductive nanoparticles produces localized plasmon oscillations with a resonant frequency that strongly depends on the composition, size, geometry, and dielectric environment. Hybrid heterostructure materials combining two or more materials in one structure represent a powerful way to achieve unique properties and multifunctionality compared to those of the individual nanoparticle components. Hybrid gold nanorods and gold nanoclusters (GNR/AuNCs) heterostructures prepared by intimate integration of GNRs with AuNCs exhibit both localized surface plasmon resonance (LSPR) property and peroxidase-like activity. It is found that the catalytic activity of the AuNC/GNR heterostructure could be remarkably enhanced by LSPR induced by photon-plasmon coupling in the visible to near-infrared (NIR) region. Meanwhile, the catalytic activity of enzyme-like AuNC/GNRs may be regulated by immunoreactions to realize specific recognition of a target analyte. Accordingly, a fast colorimetric assay within 5 min for the detection of prostate specific antigen (PSA) was developed based on a AuNC/GNRs heterostructure mask regulated by the target molecule under photon-plasmon coupling. The color intensity is inversely proportional to the PSA concentration, and quantitative analysis may be achieved in a range of 10 and 200 pg mL-1. This sensor was practically applied to detect PSA levels in prostate cancer serum samples and the determined values agreed well with those measured by the hospital using standard methods. This indicates that the AuNC/GNRs heterostructure-based assay has high accuracy for the analysis of practical samples. Moreover, the new method has the advantages of very fast determination and low sample volume requirements.

Association of Antipsychotic Drugs with Venous Thromboembolism: Data Mining of Food and Drug Administration Adverse Event Reporting System and Mendelian Randomization Analysis.

AIMS: Past observational studies have reported on the association between antipsychotic drugs and venous thromboembolism (VTE); however, the conclusions remain controversial, and its mechanisms are yet to be fully understood. Thus, in this study, we aim to determine the associations of antipsychotic drugs with VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE), and their potential mechanisms. METHODS: We first mined the adverse event signals of VTE, DVT, and PE caused by antipsychotic drugs in Food and Drug Administration Adverse Event Reporting System (FAERS). Next, we used two-sample Mendelian randomization (MR) method to investigate the association of antipsychotic drug target gene expression with VTE, DVT, and PE, using single-nucleotide polymorphisms as genetic instruments. We not only used the expression of all antipsychotic drug target genes as exposure to perform MR analyses but also analyzed the effect of single target gene expression on the outcomes. RESULTS: In the FAERS, 1694 cases of VTE events were reported by 16 drugs. However, using the MR approach, no significant association was determined between the expression of all antipsychotic target genes and VTE, DVT, or PE, either in blood or brain tissue. Although the analysis of single gene expression data showed that the expression of nine genes was associated with VTE events, these targets lacked significant pharmacological action. CONCLUSIONS: Adverse event mining results have supported the claim that antipsychotic drugs can increase the risk of VTE. However, we failed to find any genetic evidence for this causal association and potential mechanisms. Thus, vigilance is still needed for antipsychotic drug-related VTE despite the limited supporting evidence.

Mosquito E-20-Monooxygenase Gene Knockout Increases Dengue Virus Replication in Aedes aegypti Cells.

E-20-monooxygenase (E20MO) is an enzymatic product of the shade (shd) locus (cytochrome p450, E20MO). Initially discovered in Drosophila, E20MO facilitates the conversion of ecdysone (E) into 20-hydroxyecdysone (20E) and is crucial for oogenesis. Prior research has implicated 20E in growth, development, and insecticide resistance. However, little attention has been given to the association between the E20MO gene and DENV2 infection. The transcriptome of Ae. aegypti cells (Aag2 cells) infected with DENV2 revealed the presence of the E20MO gene. The subsequent quantification of E20MO gene expression levels in Aag2 cells post-DENV infection was carried out. A CRISPR/Cas9 system was utilized to create an E20MO gene knockout cell line (KO), which was then subjected to DENV infection. Analyses of DENV2 copies in KO and wild-type (WT) cells were conducted at different days post-infection (dpi). Plasmids containing E20MO were constructed and transfected into KO cells, with pre- and post-transfection viral copy comparisons. Gene expression levels of E20MO increased after DENV infection. Subsequently, a successful generation of an E20MO gene knockout cell line and the verification of code-shifting mutations at both DNA and RNA levels were achieved. Furthermore, significantly elevated DENV2 RNA copies were observed in the mid-infection phase for the KO cell line. Viral RNA copies were lower in cells transfected with plasmids containing E20MO, compared to KO cells. Through knockout and plasmid complementation experiments in Aag2 cells, the role of E20MO in controlling DENV2 replication was demonstrated. These findings contribute to our understanding of the intricate biological interactions between mosquitoes and arboviruses.

Aedes aegypti Beta-1,3-Glucan-Binding Protein Inhibits Dengue and ZIKA Virus Replication.

GNBPB6, a beta-1,3-glucan-binding protein, was identified in the transcriptome of Aedes aegypti (A. aegypti) with dengue (DENV), Zika (ZIKV), and chikungunya viruses (CHIKV). In this study, we not only clarified that DENV2 and ZIKV regulate the changes in GNBPB6 expression but also identified the relationship of this gene with viral infections. The changes in GNBPB6 expression were quantified and showed a decrease in A. aegypti cells (Aag2 cells) at 2 dpi and 3 dpi and an increase at 4 dpi and 5 dpi (p < 0.05). A significant increase was observed only at 5 dpi after DENV2 infection. Subsequently, a GNBPB6 knockout (KO) cell line was constructed using the CRISPR/Cas9 system, and the DENV2 and ZIKV RNA copies, along with cell densities, were quantified and compared between the KO and wild type (WT) cells at different dpi. The result showed that DENV2 and ZIKV RNA copies were significantly increased in the KO cell line with no significant change in cell growth. Finally, DENV2 copies decreased after GNBPB6 was complemented in the KO. In conclusion, GNBPB6 knockout and complementation in Aag2 cells revealed that GNBPB6 can inhibit the replication of both DENV2 and ZIKV. These results contribute to subsequent research on mosquito-virus interactions.

[Dosimetric comparison of left-side whole breast irradiation with IMRT and hybrid IMRT].

OBJECTIVE: To evaluate the potential dosimetric benefits and optimal indications of intensity modulated radiation therapy (IMRT) and hybrid intensity modulated radiation therapy (Hybrid IMRT) for the left side breast cancer patients after breast-conservation therapy. METHODS: Eight patients with left breast carcinoma who received breast-conservation surgery were selected for this study. Two plans were designed in 3-dimensional treatment planning system. The dose distributions of target volume and normal tissues, conformal index (CI) and heterogeneous index (HI) were analyzed by dose-volume histogram (DVH). RESULTS: The PTV coverage was the same in the two radiotherapy plans. A better dose uniformity throughout the whole breast in Hybrid IMRT plan was achieved. The CI, the percentage of PTV receiving more than 105% prescribed dose (V105%), the percentage of PTV receiving more than 110% prescribed dose (V110%), and the Dmax, Dmin and Dmean of PTV were similar in the two plans. We compared the Hybrid IMRT with IMRT: V13 of the ipsilateral lung decreased from 27.66% to 20.7%, V5 of the contralateral lung decreased from 8.01% to 2.25%, V10 and V20 of the heart decreased from 35.23% and 16.77% to 19.22% and 10.6% respectively, V5 and V10 of the contralateral breast decreased from 35% and 10.39% to 20.38% and 5.7% respectively, all with significant difference. V30 and V40 of the ipsilateral lung and V40 of the heart increased by 1.28%, 1.48%, and 2.48%, with significant difference. CONCLUSION: Hybrid IMRT is a better choice for patients whose treatment position is inaccurate or cannot be repeated well.

Corrigendum to "Remodeling tumor immunosuppressive microenvironment via a novel bioactive nanovaccines potentiates the efficacy of cancer immunotherapy" [Bioactive Mater. 16 107-119].

[This corrects the article DOI: 10.1016/j.bioactmat.2022.03.008.].

CT-based dosiomics and radiomics model predicts radiation-induced lymphopenia in nasopharyngeal carcinoma patients.

Purpose: This study aims to develop and validate a model predictive for the incidence of grade 4 radiation-induced lymphopenia (G4RIL), based on dosiomics features and radiomics features from the planning CT of nasopharyngeal carcinoma (NPC) treated by radiation therapy. Methods: The dataset of 125 NPC patients treated with radiotherapy from August 2018 to March 2019 was randomly divided into two sets-an 85-sample training set and a 40-sample test set. Dosiomics features and radiomics features of the CT image within the skull bone and cervical vertebrae were extracted. A feature selection process of multiple steps was employed to identify the features that most accurately forecast the data and eliminate superfluous or insignificant ones. A support vector machine learning classifier with correction for imbalanced data was trained on the patient dataset for prediction of RIL (positive classifier for G4RIL, negative otherwise). The model's predictive capability was gauged by gauging its sensitivity (the likelihood of a positive test being administered to patients with G4RIL) and specificity in the test set. The area beneath the ROC curve (AUC) was utilized to explore the association of characteristics with the occurrence of G4RIL. Results: Three clinical features, three dosiomics features, and three radiomics features exhibited significant correlations with G4RIL. Those features were then used for model construction. The combination model, based on nine robust features, yielded the most impressive results with an ACC value of 0.88 in the test set, while the dosiomics model, with three dosiomics features, had an ACC value of 0.82, the radiomics model, with three radiomics features, had an ACC value of 0.82, and the clinical model, with its initial features, had an ACC value of 0.6 for prediction performance. Conclusion: The findings show that radiomics and dosiomics features are correlated with the G4RIL of NPC patients. The model incorporating radiomics features and dosiomics features from planning CT can predict the incidence of G4RIL in NPC patients.

A Machine Learning-Based Predictive Model of Epidermal Growth Factor Mutations in Lung Adenocarcinomas.

Data from 758 patients with lung adenocarcinoma were retrospectively collected. All patients had undergone computed tomography imaging and EGFR gene testing. Radiomic features were extracted using the medical imaging tool 3D-Slicer and were combined with the clinical features to build a machine learning prediction model. The high-dimensional feature set was screened for optimal feature subsets using principal component analysis (PCA) and the least absolute shrinkage and selection operator (LASSO). Model prediction of EGFR mutation status in the validation group was evaluated using multiple classifiers. We showed that six clinical features and 622 radiomic features were initially collected. Thirty-one radiomic features with non-zero correlation coefficients were obtained by LASSO regression, and 24 features correlated with label values were obtained by PCA. The shared radiomic features determined by these two methods were selected and combined with the clinical features of the respective patient to form a subset of features related to EGFR mutations. The full dataset was partitioned into training and test sets at a ratio of 7:3 using 10-fold cross-validation. The area under the curve (AUC) of the four classifiers with cross-validations was: (1) K-nearest neighbor (AUCmean = 0.83, Acc = 81%); (2) random forest (AUCmean = 0.91, Acc = 83%); (3) LGBM (AUCmean = 0.94, Acc = 88%); and (4) support vector machine (AUCmean = 0.79, Acc = 83%). In summary, the subset of radiographic and clinical features selected by feature engineering effectively predicted the EGFR mutation status of this NSCLC patient cohort.

Correction: Chemo-photodynamic combined gene therapy and dual-modal cancer imaging achieved by pH-responsive alginate/chitosan multilayer-modified magnetic mesoporous silica nanocomposites.

Correction for 'Chemo-photodynamic combined gene therapy and dual-modal cancer imaging achieved by pH-responsive alginate/chitosan multilayer-modified magnetic mesoporous silica nanocomposites' by Hong Yang et al., Biomater. Sci., 2017, 5, 1001-1013, https://doi.org/10.1039/c7bm00043j.