Publications by authors named "Lei Xing"

578 Publications

The circACTN4 interacts with FUBP1 to promote tumorigenesis and progression of breast cancer by regulating the expression of proto-oncogene MYC.

Mol Cancer 2021 Jun 11;20(1):91. Epub 2021 Jun 11.

Department of Cell Biology and Genetics, Chongqing Medical University, #1 Yixueyuan Road, Chongqing, 400016, China.

Background: Recent studies have revealed that circular RNAs (circRNAs) play significant roles in the occurrence and development of many kinds of cancers including breast cancer (BC). However, the potential functions of most circRNAs and the molecular mechanisms underlying progression of BC remain elusive.

Method: Here, Circular RNA microarray was executed in 4 pairs of breast cancer tissues and para-cancer tissues. The expression and prognostic significance of circACTN4 in BC cells and tissues were determined by qRT-PCR and in situ hybridization. Gain-and loss-of-function experiments were implemented to observe the impacts of circACTN4 on the growth, invasion, and metastasis of BC cells in vitro and in vivo. Mechanistically, chromatin immunoprecipitation, luciferase reporter, RNA pulldown, mass spectrum, RNA immunoprecipitation, fluorescence in situ hybridization and co-immunoprecipitation assays were executed.

Results: CircACTN4 was significantly upregulated in breast cancer tissues and cells, its expression was correlated with clinical stage and poor prognosis of patients with BC. Ectopic expression of circACTN4 strikingly facilitated the growth, invasion, and metastasis of breast cancer cells in vitro and in vivo. Whereas knockdown of circACTN4 revealed opposite roles. CircACTN4 was mainly distributed in the nucleus. Further mechanistic research proved that circACTN4 could competitively bind to far upstream element binding protein 1 (FUBP1) to prevent the combination between FUBP1 and FIR, thereby activating MYC transcription and facilitating tumor progression of breast cancer. Furthermore, we found that upstream transcription factor 2 (USF2) might promote the biogenesis of circACTN4.

Conclusion: Our findings uncover a pivotal mechanism that circACTN4 mediated by USF2 might interact with FUBP1 to promote the occurrence and development of breast cancer via enhancing the expression of MYC. CircACTN4 could be a novel potential target for diagnosis and treatment of breast cancer.
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http://dx.doi.org/10.1186/s12943-021-01383-xDOI Listing
June 2021

Antigenic Drift of the Hemagglutinin from an Influenza A (H1N1) pdm09 Clinical Isolate Increases its Pathogenicity In Vitro.

Virol Sin 2021 Jun 9. Epub 2021 Jun 9.

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510180, China.

The influenza A (H1N1) pdm09 virus emerged in 2009 and has been continuously circulating in humans for over ten years. Here, we analyzed a clinical influenza A (H1N1) pdm09-infected patient case hospitalized for two months in Guangdong (from December 14, 2019 to February 15, 2020). This isolate, named A/Guangdong/LCF/2019 (LCF/19), was genetically sequenced, rescued by reverse genetics, and phylogenetically analyzed in the context of other relevant pdm09 isolates. Compared with earlier isolates, this pdm09 virus's genetic sequence contains four substitutions, S186P, T188I, D190A, and Q192E, of the hemagglutinin (HA) segment at position 186-192 (H3 numbering) in the epitope Sb, and two of which are located at the 190-helix. Phylogenetic analysis indicated that the epitope Sb started undergoing a rapid antigenic change in 2018. To characterize the pathogenicity of this novel substitution motif, a panel of reassortant viruses containing the LCF/2019 HA segment or the chimeric HA segment with the four substitutions were rescued. Kinetic growth data revealed that the reassortant viruses, including the LCF/2019 with the PTIAAQE substitution, propagated faster than those rescued ones having the STTADQQ motif in the epitope Sb in Madin-Darby Canine Kidney (MDCK) cells. The HI test showed that the binding activity of escape mutant to 2018 pdm09 sera was weaker than GLW/2018, suggesting that old vaccines might not effectively protect people from infection. Due to the difference in the selection of vaccine strains, people vaccinated in the southern hemisphere could still suffer a severe infection if infected with this antigenic drift pdm09 virus.
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http://dx.doi.org/10.1007/s12250-021-00401-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188537PMC
June 2021

Recognize the role of CD146/MCAM in the osteosarcoma progression: an in vitro study.

Cancer Cell Int 2021 Jun 8;21(1):300. Epub 2021 Jun 8.

Department of Orthopedic Surgery, The First Affiliated Hospital, Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, 150001, China.

Background: Osteosarcoma (OS) is a common malignant bone tumor with poor prognosis. We previously reviewed that CD146 is correlated with multiple cancer progression, while its impact on OS is currently not systematically studied.

Methods: MG63 was transfected with lentivirus to express CD146 ectopically, and anti-CD146 neutralizing antibody ab75769 was used to inhibit 143B. Cyclic migration of MG63 and co-culture between MG63 and 143B were used to explore the role of OS malignancy in CD146 expression. The effect of OS cell medium (CM) on endothelium behaviors was assessed, and the expression changes of CD146 before and after co-culture of endothelium and OS were evaluated. Finally, the expression of CD146 in OS was detected under different culture conditions, including hyperoxia, low oxygen, high glucose and low glucose conditions.

Results: CD146 promoted the colony formation, migration, invasion and homotypic adhesion of OS cells, and reducing the concentration of soluble CD146 in the OS medium inhibited the proliferation, migration and lumen formation of the cultured endothelium. However, CD146 did not affect the adhesion between OS and endothelium, nor did co-culture of both sides affect the CD146 expression. Similarly, the proliferation, migration and CD146 expression of MG63 remained unchanged after many cycles of migration itself, as did its co-culture with 143B for expressing CD146. In addition, we also showed that high glucose promoted the expression of CD146 in OS, while hypoxia had the opposite effect.

Conclusions: These findings demonstrate that CD146 promotes OS progression by mediating pro-tumoral and angiogenic effects. Thus, CD146 could be a potential therapeutic target for OS, especially for OS patients with diabetes.
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http://dx.doi.org/10.1186/s12935-021-02006-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186124PMC
June 2021

Long non-coding RNA LINC01116 is activated by EGR1 and facilitates lung adenocarcinoma oncogenicity via targeting miR-744-5p/CDCA4 axis.

Cancer Cell Int 2021 Jun 5;21(1):292. Epub 2021 Jun 5.

Department of Thoracic Surgery, The First Hospital of Jilin University, No. 71, Xinmin Road, Changchun, 130021, Jilin, China.

Background: Lung adenocarcinoma (LAD) is one of the most frequently diagnosed pathological categories of human lung cancer. Nevertheless, the link between long non-coding RNA (lncRNA) LINC01116 and LAD remains poorly investigated.

Methods: QRT-PCR and western blot were applied for quantifying the expression of RNAs and proteins. Both functional experiments assays in vitro and xenografts model in vivo were implemented for analyzing LINC01116 function in LAD while molecular relationship among RNAs was investigated via mechanism experiments.

Results: LINC01116 was expressed at an abnormally high level in LAD, which was induced by transcription activator EGR1. LINC01116 depletion restrained proliferation, migration and invasion, yet facilitated apoptosis of LAD cells. MiR-744-5p could bind to LINC01116. MiR-744-5p inhibitor reversed the inhibitory effects of silencing LINC01116 on LAD malignant behaviors. In addition, cell division cycle-associated protein 4 (CDCA4) shared binding sites with miR-744-5p. Silencing LINC01116 elicited decline in CDCA4 mRNA and protein levels. Moreover, CDCA4 up-regulation could counteract the biological effects of LINC01116 knockdown on LAD cells.

Conclusion: Our data revealed that LINC01116 promoted malignant behaviors of LAD cells by targeting miR-744-5p/CDCA4 axis, implying the theoretical potential of LINC01116 as a novel target for LAD treatment.
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http://dx.doi.org/10.1186/s12935-021-01994-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180037PMC
June 2021

Multiphysics Modeling and Simulation of Subcutaneous Injection and Absorption of Biotherapeutics: Sensitivity Analysis.

Pharm Res 2021 Jun 2. Epub 2021 Jun 2.

Department of Industrial and Physical Pharmacy, Purdue University, 525 Stadium Mall Dr. RHPH Building, Indiana, 47907, West Lafayette, USA.

Purpose: A multiphysics simulation model was recently developed to capture major physical and mechanical processes of local drug transport and absorption kinetics of subcutaneously injected monoclonal antibody (mAb) solutions. To further explore the impact of individual drug attributes and tissue characteristics on the tissue biomechanical response and drug mass transport upon injection, sensitivity analysis was conducted and reported.

Method: Various configurations of injection conditions, drug-associated attributes, and tissue properties were simulated with the developed multiphysics model. Simulation results were examined with regard to tissue deformation, porosity change, and spatiotemporal distributions of pressure, interstitial fluid flow, and drug concentration in the tissue.

Results: Injection conditions and tissue properties were found influential on the mechanical response of tissue and interstitial fluid velocity to various extents, leading to distinct drug concentration profiles. Intrinsic tissue porosity, lymphatic vessel density, and drug permeability through the lymphatic membrane were particularly essential in determining the local absorption rate of an mAb injection.

Conclusion: The sensitivity analysis study may shed light on the product development of an mAb formulation, as well as on the future development of the simulation method.
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http://dx.doi.org/10.1007/s11095-021-03062-4DOI Listing
June 2021

A Harmless-Harmful Switchable and Uninterrupted Laccase-Instructed Killer for Activatable Chemodynamic Therapy.

Adv Mater 2021 Jun 1:e2100114. Epub 2021 Jun 1.

State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.

Chemodynamic therapy (CDT) employs Fenton catalysts to kill cancer cells by converting intracellular hydrogen peroxide (H O ) into hydroxyl radicals (OH•). Although many studies on H O supplementation have been conducted to improve the therapeutic effect of CDT, few studies have focused on the application of superoxide radical (O ) in CDT, which may result in better efficacy. A major concern about O -mediated CDT is its tendency to induce serious oxidative damage to normal tissues, which may be addressed by using a degradable O scavenger. Here, a harmless-harmful switchable and uninterrupted laccase (LAC)-instructed killer (HULK) is constructed, which is the first CDT agent accelerated by LAC-instructed O generation and possesses a harmless-harmful switchable effect because of the photodegradation of the O scavenger iron-chlorin e6 (FeCe6). LAC-instructed substrate oxidation effectively catalyzes O production with the help of intracellular reduction, thereby promoting the conversion of Fe to Fe , accelerating the generation of OH•, and inducing tumor cell apoptosis and necrosis. The introduced O scavenger FeCe6 is quickly photodegraded during irradiation, while LAC-instructed O generation proceeds as before, resulting in activatable CDT. This work not only provides the first strategy for LAC-instructed O generation but also presents new insight into activatable CDT.
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http://dx.doi.org/10.1002/adma.202100114DOI Listing
June 2021

Deep Neural Network with Consistency Regularization of Multi-Output Channels for Improved Tumor Detection and Delineation.

IEEE Trans Med Imaging 2021 May 28;PP. Epub 2021 May 28.

Deep learning is becoming an indispensable tool for imaging applications, such as image segmentation, classification, and detection. In this work, we reformulate a standard deep learning problem into a new neural network architecture with multi-output channels, which reflects different facets of the objective, and apply the deep neural network to improve the performance of image segmentation. By adding one or more interrelated auxiliary-output channels, we impose an effective consistency regularization for the main task of pixelated classification (i.e., image segmentation). Specifically, multi-output-channel consistency regularization is realized by residual learning via additive paths that connect main-output channel and auxiliary-output channels in the network. The method is evaluated on the detection and delineation of lung and liver tumors with public data. The results clearly show that multi-output-channel consistency implemented by residual learning improves the standard deep neural network. The proposed framework is quite broad and should find widespread applications in various deep learning problems.
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http://dx.doi.org/10.1109/TMI.2021.3084748DOI Listing
May 2021

Zafirlukast promotes mitochondrial respiration by stimulating mitochondrial biogenesis in human bronchial epithelial cells.

J Mol Histol 2021 May 11. Epub 2021 May 11.

Department of Thoracic Surgery, The First Hospital of Jilin University, No. 71 Xinmin Street, Chaoyang District, Changchun, Jilin Province, 130021, China.

Lung diseases, including asthma, pose a serious global health issue. Loss of mitochondrial function and decreased mitochondrial biogenesis play pivotal roles in the initiation and progression of chronic lung diseases. Thus, maintaining mitochondrial function and homeostasis is an important treatment goal. Zafirlukast is a CysLTR1 antagonist that is widely used as an adjuvant treatment for asthma. In the present study, we investigated the effects of zafirlukast in vitro using human bronchial epithelial cells (BECs). We performed measurements of oxygen consumption and bioenergetics and found that zafirlukast increased mitochondrial respiration and biogenesis in human BECs as evidenced by increased mitochondrial mass and mtDNA/nDNA. Through real-time PCR and western blot analysis, we found that zafirlukast significantly increased the expression of PGC-1α, NRF1, and TFAM at both the mRNA and protein levels. Finally, we determined that these effects are mediated through CREB signaling and that inhibition of CREB with its specific inhibitor H89 abolished the effects of zafirlukast described above. Thus, zafirlukast might have potential in enhancing mitochondrial function by promoting mitochondrial biogenesis in human bronchial epithelial cells through upregulating the expression of PGC-1α and activating the CREB pathway.
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http://dx.doi.org/10.1007/s10735-021-09974-0DOI Listing
May 2021

Expression of human-specific ARHGAP11B in mice leads to neocortex expansion and increased memory flexibility.

EMBO J 2021 May 3:e107093. Epub 2021 May 3.

Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.

Neocortex expansion during human evolution provides a basis for our enhanced cognitive abilities. Yet, which genes implicated in neocortex expansion are actually responsible for higher cognitive abilities is unknown. The expression of human-specific ARHGAP11B in embryonic/foetal mouse, ferret and marmoset neocortex was previously found to promote basal progenitor proliferation, upper-layer neuron generation and neocortex expansion during development, features commonly thought to contribute to increased cognitive abilities. However, a key question is whether this phenotype persists into adulthood and if so, whether cognitive abilities are indeed increased. Here, we generated a transgenic mouse line with physiological ARHGAP11B expression that exhibits increased neocortical size and upper-layer neuron numbers persisting into adulthood. Adult ARHGAP11B-transgenic mice showed altered neurobehaviour, notably increased memory flexibility and a reduced anxiety level. Our data are consistent with the notion that neocortex expansion by ARHGAP11B, a gene implicated in human evolution, underlies some of the altered neurobehavioural features observed in the transgenic mice, such as the increased memory flexibility, a neocortex-associated trait, with implications for the increase in cognitive abilities during human evolution.
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http://dx.doi.org/10.15252/embj.2020107093DOI Listing
May 2021

MR to ultrasound image registration with segmentation-based learning for HDR prostate brachytherapy.

Med Phys 2021 Apr 27. Epub 2021 Apr 27.

Department of Radiation Oncology, Stanford University, Stanford, CA, 94305, USA.

Purpose: Propagation of contours from high-quality magnetic resonance (MR) images to treatment planning ultrasound (US) images with severe needle artifacts is a challenging task, which can greatly aid the organ contouring in high dose rate (HDR) prostate brachytherapy. In this study, a deep learning approach was developed to automatize this registration procedure for HDR brachytherapy practice.

Methods: Because of the lack of training labels and difficulty of accurate registration from inferior image quality, a new segmentation-based registration framework was proposed for this multi-modality image registration problem. The framework consisted of two segmentation networks and a deformable registration network, based on the weakly -supervised registration strategy. Specifically, two 3D V-Nets were trained for the prostate segmentation on the MR and US images separately, to generate the weak supervision labels for the registration network training. Besides the image pair, the corresponding prostate probability maps from the segmentation were further fed to the registration network to predict the deformation matrix, and an augmentation method was designed to randomly scale the input and label probability maps during the registration network training. The overlap between the deformed and fixed prostate contours was analyzed to evaluate the registration accuracy. Three datasets were collected from our institution for the MR and US image segmentation networks, and the registration network learning, which contained 121, 104, and 63 patient cases, respectively.

Results: The mean Dice similarity coefficient (DSC) results of the two prostate segmentation networks are 0.86 ± 0.05 and 0.90 ± 0.03, for MR images and the US images after the needle insertion, respectively. The mean DSC, center-of-mass (COM) distance, Hausdorff distance (HD), and averaged symmetric surface distance (ASSD) results for the registration of manual prostate contours were 0.87 ± 0.05, 1.70 ± 0.89 mm, 7.21 ± 2.07 mm, 1.61 ± 0.64 mm, respectively. By providing the prostate probability map from the segmentation to the registration network, as well as applying the random map augmentation method, the evaluation results of the four metrics were all improved, such as an increase in DSC from 0.83 ± 0.08 to 0.86 ± 0.06 and from 0.86 ± 0.06 to 0.87 ± 0.05, respectively.

Conclusions: A novel segmentation-based registration framework was proposed to automatically register prostate MR images to the treatment planning US images with metal artifacts, which not only largely saved the labor work on the data preparation, but also improved the registration accuracy. The evaluation results showed the potential of this approach in HDR prostate brachytherapy practice.
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http://dx.doi.org/10.1002/mp.14901DOI Listing
April 2021

Pt-based (Zn, Cu) nanodendrites with enhanced catalytic efficiency and durability toward methanol electro-oxidation via trace Ir-doping engineering.

J Colloid Interface Sci 2021 Sep 9;598:126-135. Epub 2021 Apr 9.

Institute for Energy Research, Jiangsu University, 301 Xuefu Road, Zhenjiang 212013, PR China. Electronic address:

Pt-based alloy nanomaterials with nanodendrites (NDs) structures are efficient electrocatalysts for methanol oxidation reaction (MOR), however their durability is greatly limited by the issue of transition metals dissolution. In this work, a facile trace Ir-doping strategy was proposed to fabricate Ir-PtZn and Ir-PtCu alloy NDs catalysts in aqueous medium, which significantly improved the electrocatalytic activity and durability for MOR. The as-prepared Ir-PtZn/Cu NDs catalysts showed distinct dendrites structures with the averaged diameter of 4.1 nm, and trace Ir doping subsequently improved the utilization of Pt atoms and promoted the oxidation efficiency of methanol. The electrochemical characterizations further demonstrated that the obtained Ir-PtZn/Cu NDs possessed enhanced mass activities of nearly 1.23 and 1.28-fold higher than those of undoped PtZn and PtCu, and approximately 2.35 and 2.67-fold higher than that of Pt/C in acid medium. More excitingly, after long-term durability test, the proposed Ir-PtZn and Ir-PtCu NDs still retained about 88.9% and 91.6% of its initial mass activities, which further highlights the key role of Ir-doping in determining catalyst performance. This work suggests that trace Ir-doping engineering could be a promising way to develop advanced electrocatalysts toward MOR for direct methanol fuel cell (DMFC) applications.
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http://dx.doi.org/10.1016/j.jcis.2021.04.014DOI Listing
September 2021

Rotation-oriented Collaborative Self-supervised Learning for Retinal Disease Diagnosis.

IEEE Trans Med Imaging 2021 Apr 23;PP. Epub 2021 Apr 23.

The automatic diagnosis of various conventional ophthalmic diseases from fundus images is important in clinical practice. However, developing such automatic solutions is challenging due to the requirement of a large amount of training data and the expensive annotations for medical images. This paper presents a novel self-supervised learning framework for retinal disease diagnosis to reduce the annotation efforts by learning the visual features from the unlabeled images. To achieve this, we present a rotation-oriented collaborative method that explores rotation-related and rotation-invariant features, which capture discriminative structures from fundus images and also explore the invariant property used for retinal disease classification. We evaluate the proposed method on two public benchmark datasets for retinal disease classification. The experimental results demonstrate that our method outperforms other self-supervised feature learning methods (around 4.2% area under the curve (AUC)). With a large amount of unlabeled data available, our method can surpass the supervised baseline for pathologic myopia (PM) and is very close to the supervised baseline for age-related macular degeneration (AMD), showing the potential benefit of our method in clinical practice.
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http://dx.doi.org/10.1109/TMI.2021.3075244DOI Listing
April 2021

Ginkgo biloba extract improves cognitive function and increases neurogenesis by reducing Aβ pathology in 5×FAD mice.

Am J Transl Res 2021 15;13(3):1471-1482. Epub 2021 Mar 15.

Department of Neurology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China No 17 Lvjiang Road, Hefei 230001, Anhui, China.

Previous studies have indicated that the generation of newborn hippocampal neurons is impaired in the early phase of Alzheimer's disease (AD). A potential therapeutic strategy being pursued for the treatment of AD is increasing the number of newborn neurons in the adult hippocampus. Recent studies have demonstrated that ginkgo biloba extract (EGb 761) plays a neuroprotective role by preventing memory loss in many neurodegenerative diseases. However, the extent of EGb 761's protective role in the AD process is unclear. In this study, different doses of EGb 761 (0, 10, 20, and 30 mg/kg; intraperitoneal injections once every day for four months) were tested on 5×FAD mice. After consecutive 4-month injections, mice were tested in learning memory tasks, Aβ, and neurogenesis in the dentate gyrus (DG) of hippocampus and morphological characteristics of neurons in DG of hippocampus. Results indicated that EGb 761 (20 and 30 mg/kg) ameliorated memory deficits. Further analysis indicated that EGb 761 can reduce the number of Aβ positive signals in 5×FAD mice, increase the number of newborn neurons, and increase dendritic branching and density of dendritic spines in 5×FAD mice compared to nontreated 5×FAD mice. It was concluded that EGb 761 plays a protective role in the memory deficit of 5×FAD mice.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014356PMC
March 2021

Multiphysics Modeling and Simulation of Subcutaneous Injection and Absorption of Biotherapeutics: Model Development.

Pharm Res 2021 Apr 2;38(4):607-624. Epub 2021 Apr 2.

Department of Industrial and Physical Pharmacy, Purdue University, 525 Stadium Mall Dr., RHPH Building, West Lafayette, Indiana, 47907, USA.

Purpose: Many monoclonal antibodies (mAbs) are administered via subcutaneous (SC) injection. Local transport and absorption kinetics and mechanisms, however, remain poorly understood. A multiphysics computational model was developed to simulate the injection and absorption processes of a protein solution in the SC tissue.

Methods: Quantitative relationships among tissue properties and transport behaviors of an injected solution were described by respective physical laws. SC tissue was treated as a 3-dimensional homogenous, poroelastic medium, in which vasculatures and lymphatic vessels were implicitly treated. Tissue deformation was considered, and interstitial fluid flow was modeled by Darcy's law. Transport of the drug mass was described based on diffusion and advection, which was integrated with tissue mechanics and interstitial fluid dynamics.

Results: Injection and absorption of albumin and IgG solutions were simulated. Upon injection, a sharp rise in tissue pressure, porosity, and fluid velocity could be observed at the injection tip. Largest tissue deformation appeared at the model surface. Transport of drug mass out of the injection zone was minimal. Absorption by local lymphatics was found to last several weeks.

Conclusions: A bottom-up method was developed to simulate drug transport and absorption of protein solutions in skin tissue base on physical principles. The results appear to match experimental observations.
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http://dx.doi.org/10.1007/s11095-021-03032-wDOI Listing
April 2021

Social support, self-worth, and subjective well-being in older adults of rural China: a cross-sectional study.

Psychol Health Med 2021 Mar 29:1-7. Epub 2021 Mar 29.

College of Mechanical Science and Engineering, Northeast Petroleum University, Daqing, China.

This study explored the relationship between social support and subjective well-being of the rural Chinese older adults and investigated whether self-worth could mediate this association. A total number of 356 older adults from rural areas of China were investigated using three scales. The results were as follows: there were significant correlations between social support, self-worth, and subjective well-being (where < 0.01 in all of them). Bootstrapping mediation analyses indicated that self-worth partly mediated the association between social support and subjective well-being. Accordingly, social support and self-worth are important targets for improving the subjective well-being level of the rural older adults.
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http://dx.doi.org/10.1080/13548506.2021.1905861DOI Listing
March 2021

Selenium uptake and simultaneous catalysis of sulfite oxidation in ammonia-based desulfurization.

J Environ Sci (China) 2021 May 16;103:207-218. Epub 2020 Nov 16.

Hebei Key Lab of Power Plant Flue Gas Multi-Pollutants Control, Department of Environmental Science and Engineering, North China Electric Power University, Baoding, 071003, PR China. Electronic address:

Accelerating the (NH)SO oxidation gives rise to the reclaiming of byproduct, while there are secondary environmental risks from reduction of the coexisted selenium species by sulfite. In this study, a bi-functional Co-SBA-15-SH, were synthesized through Co impregnation and sulfhydryl (-SH) decoration, which can simultaneously uptake Se and accelerate sulfite oxidation efficiently. Meanwhile, the adsorption kinetics and migration mechanism of Se species were revealed through characterization and density functional calculations, with maximum adsorption capacity of 223 mg/g. The inhibition of Se re-emission and poisonous effect of Se on sulfite oxidation was also investigated. Using the findings of this study, the ammonia desulfurization can be improved by enabling purification of the byproduct and lowering the toxicity of effluent by removing toxic pollutants.
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http://dx.doi.org/10.1016/j.jes.2020.10.012DOI Listing
May 2021

Prior-image-based CT reconstruction using attenuation-mismatched priors.

Phys Med Biol 2021 Mar 17;66(6):064007. Epub 2021 Mar 17.

Department of Radiation Oncology, Stanford University School of Medicine, California, United States of America. Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, United States of America.

Prior-image-based reconstruction (PIBR) methods are powerful tools for reducing radiation doses and improving the image quality of low-dose computed tomography (CT). Apart from anatomical changes, prior and current images can also have different attenuations because they originated from different scanners or from the same scanner but with different x-ray beam qualities (e.g., kVp settings, beam filters) during data acquisition. In such scenarios, with attenuation-mismatched priors, PIBR is challenging. In this work, we investigate a specific PIBR method, called statistical image reconstruction, using normal-dose image-induced nonlocal means regularization (SIR-ndiNLM), to address PIBR with such attenuation-mismatched priors and achieve quantitative low-dose CT imaging. We propose two corrective schemes for the original SIR-ndiNLM method, (1) a global histogram-matching approach and (2) a local attenuation correction approach, to account for the attenuation differences between the prior and current images in PIBR. We validate the efficacy of the proposed schemes using images acquired from dual-energy CT scanners to simulate attenuation mismatches. Meanwhile, we utilize different CT slices to simulate anatomical mismatches or changes between the prior and the current low-dose image. We observe that the original SIR-ndiNLM introduces artifacts to the reconstruction when an attenuation-mismatched prior is used. Furthermore, we find that a larger attenuation mismatch between the prior and current images results in more severe artifacts in the SIR-ndiNLM reconstruction. Our two proposed corrective schemes enable SIR-ndiNLM to effectively handle the attenuation mismatch and anatomical changes between the two images and successfully eliminate the artifacts. We demonstrate that the proposed techniques permit SIR-ndiNLM to leverage the attenuation-mismatched prior and achieve quantitative low-dose CT reconstruction from both low-flux and sparse-view data acquisitions. This work permits robust and reliable PIBR for CT data acquired using different beam settings.
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http://dx.doi.org/10.1088/1361-6560/abe760DOI Listing
March 2021

A robotically assisted 3D printed quality assurance lung phantom for Calypso.

Phys Med Biol 2021 Apr 6;66(7). Epub 2021 Apr 6.

Department of Radiation Oncology, School of Medicine, Stanford University, Stanford, California, United States of America.

. Radiation dose delivered to targets located near the upper-abdomen or in the thorax are significantly affected by respiratory-motion. Relatively large-margins are commonly added to compensate for this motion, limiting radiation-dose-escalation. Internal-surrogates of target motion, such as a radiofrequency (RF) tracking system, i.e. CalypsoSystem, are used to overcome this challenge and improve normal-tissue sparing. RF tracking systems consist of implanting transponders in the vicinity of the tumor to be tracked using radiofrequency-waves. Unfortunately, although the manufacture provides a universal quality-assurance (QA) phantom, QA-phantoms specifically for lung-applications are limited, warranting the development of alternative solutions to fulfil the tests mandated by AAPM's TG142. Accordingly, our objective was to design and develop a motion-phantom to evaluate Calypso for lung-applications that allows the CalypsoBeacons to move in different directions to better simulate trulung-motion.A Calypso lung QA-phantom was designed, and 3D-printed. The design consists of three independent arms where the transponders were attached. A pinpoint-chamber with a buildup-cap was also incorporated. A 4-axis robotic arm was programmed to drive the motion-phantom to mimic breathing. After acquiring a four-dimensional-computed-tomography (4DCT) scan of the motion-phantom, treatment-plans were generated and delivered on a Varian TrueBeamwith Calypso capabilities. Stationary and gated-treatment plans were generated and delivered to determine the dosimetric difference between gated and non-gated treatments. Portal cine-images were acquired to determine the temporal-accuracy of delivery by calculating the difference between the observed versus expected transponders locations with the known speed of the transponders' motion.Dosimetric accuracy is better than the TG142 tolerance of 2%. Temporal accuracy is greater than, TG142 tolerance of 100 ms for beam-on, but less than 100 ms for beam-hold.The robotic QA-phantom designed and developed in this study provides an independent phantom for performing Calypso lung-QA for commissioning and acceptance testing of Calypso for lung treatments.
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http://dx.doi.org/10.1088/1361-6560/abebaaDOI Listing
April 2021

Estimating dual-energy CT imaging from single-energy CT data with material decomposition convolutional neural network.

Med Image Anal 2021 05 16;70:102001. Epub 2021 Feb 16.

Stanford Cancer Center, 875 Blake Wilbur Dr, Palo Alto, CA, US.

Dual-energy computed tomography (DECT) is of great significance for clinical practice due to its huge potential to provide material-specific information. However, DECT scanners are usually more expensive than standard single-energy CT (SECT) scanners and thus are less accessible to undeveloped regions. In this paper, we show that the energy-domain correlation and anatomical consistency between standard DECT images can be harnessed by a deep learning model to provide high-performance DECT imaging from fully-sampled low-energy data together with single-view high-energy data. We demonstrate the feasibility of the approach with two independent cohorts (the first cohort including contrast-enhanced DECT scans of 5753 image slices from 22 patients and the second cohort including spectral CT scans without contrast injection of 2463 image slices from other 22 patients) and show its superior performance on DECT applications. The deep-learning-based approach could be useful to further significantly reduce the radiation dose of current premium DECT scanners and has the potential to simplify the hardware of DECT imaging systems and to enable DECT imaging using standard SECT scanners.
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http://dx.doi.org/10.1016/j.media.2021.102001DOI Listing
May 2021

Calibrated uncertainty estimation for interpretable proton computed tomography image correction using Bayesian deep learning.

Phys Med Biol 2021 Mar 16;66(6):065029. Epub 2021 Mar 16.

Department of Radiation Oncology, Stanford University, Stanford, CA 94305-5847, United States of America. Global Center for Biomedical Science and Engineering, Faculty of Medicine, Hokkaido University, Sapporo 060-8648, Japan.

Integrated-type proton computed tomography (pCT) measures proton stopping power ratio (SPR) images for proton therapy treatment planning, but its image quality is degraded due to noise and scatter. Although several correction methods have been proposed, techniques that include estimation of uncertainty are limited. This study proposes a novel uncertainty-aware pCT image correction method using a Bayesian convolutional neural network (BCNN). A DenseNet-based BCNN was constructed to predict both a corrected SPR image and its uncertainty from a noisy SPR image. A total 432 noisy SPR images of 6 non-anthropomorphic and 3 head phantoms were collected with Monte Carlo simulations, while true noise-free images were calculated with known geometric and chemical components. Heteroscedastic loss and deep ensemble techniques were performed to estimate aleatoric and epistemic uncertainties by training 25 unique BCNN models. 200-epoch end-to-end training was performed for each model independently. Feasibility of the predicted uncertainty was demonstrated after applying two post-hoc calibrations and calculating spot-specific path length uncertainty distribution. For evaluation, accuracy of head SPR images and water-equivalent thickness (WET) corrected by the trained BCNN models was compared with a conventional method and non-Bayesian CNN model. BCNN-corrected SPR images represent noise-free images with high accuracy. Mean absolute error in test data was improved from 0.263 for uncorrected images to 0.0538 for BCNN-corrected images. Moreover, the calibrated uncertainty represents accurate confidence levels, and the BCNN-corrected calibrated WET was more accurate than non-Bayesian CNN with high statistical significance. Computation time for calculating one image and its uncertainties with 25 BCNN models is 0.7 s with a consumer grade GPU. Our model is able to predict accurate pCT images as well as two types of uncertainty. These uncertainties will be useful to identify potential cause of SPR errors and develop a spot-specific range margin criterion, toward elaboration of uncertainty-guided proton therapy.
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http://dx.doi.org/10.1088/1361-6560/abe956DOI Listing
March 2021

Progress in drug delivery system for fibrosis therapy.

Asian J Pharm Sci 2021 Jan 17;16(1):47-61. Epub 2020 Jul 17.

State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China.

Fibrosis is a necessary process in the progression of chronic disease to cirrhosis or even cancer, which is a serious disease threatening human health. Recent studies have shown that the early treatment of fibrosis is turning point and particularly important. Therefore, how to reverse fibrosis has become the focus and research hotspot in recent years. So far, the considerable progress has been made in the development of effective anti-fibrosis drugs and targeted drug delivery. Moreover, the existing research results will lay the foundation for more breakthrough delivery systems to achieve better anti-fibrosis effects. Herein, this review summaries anti-fibrosis delivery systems focused on three major organ fibrotic diseases such as liver, pulmonary, and renal fibrosis accompanied by the elaboration of relevant pathological mechanisms, which will provide inspiration and guidance for the design of fibrosis drugs and therapeutic systems in the future.
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http://dx.doi.org/10.1016/j.ajps.2020.06.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878446PMC
January 2021

Prior-image-based CT reconstruction using attenuation mismatched prior.

Phys Med Biol 2021 Feb 17. Epub 2021 Feb 17.

Department of Radiation Oncology, Stanford University Medical Center, 875 Blake Wilbur Drive, Stanford, California, CA94305-5847, Stanford, California, 94305-5847, UNITED STATES.

Prior-image-based reconstruction (PIBR) methods are powerful in reducing radiation dose and improving image quality for low-dose CT. Besides anatomical changes, the prior and current images can also have different attenuation due to different scanners or the same scanner but with different x-ray beam quality (e.g., kVp setting, beam filtration) during data acquisitions. PIBR is challenged in such scenarios with attenuation mismatched prior. In this work, we investigate a specific PIBR method, called statistical image reconstruction using normal dose image induced nonlocal means regularization (SIR-ndiNLM), to address PIBR with such attenuation mismatched prior and achieve quantitative low-dose CT imaging. We proposed two corrective schemes for the original SIR-ndiNLM method, 1) a global histogram matching approach and 2) a local attenuation correction approach, to account for the attenuation differences between the prior and current images in PIBR. We validated the efficacy of the proposed schemes using images acquired from dual-energy CT scanners to emulate attenuation mismatches. Meanwhile, we utilized different CT slices to emulate anatomical mismatches/changes between the prior and the current low-dose images. We observed that the original SIR-ndiNLM introduces artifacts to the reconstruction when using attenuation mismatched prior. Furthermore, we found that larger attenuation mismatch between the prior and current images results in more severe artifacts in the SIR-ndiNLM reconstruction. Our proposed two corrective schemes enabled SIR-ndiNLM to effectively handle attenuation mismatch and anatomical changes between two images and successfully eliminate the artifacts. We demonstrated that the proposed techniques permit SIR-ndiNLM to leverage the attenuation mismatched prior and achieve quantitative low-dose CT reconstruction from both low-flux and sparse-view data acquisitions. This work permits robust and reliable PIBR for CT data acquired using different beam settings.
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http://dx.doi.org/10.1088/1361-6560/abe760DOI Listing
February 2021

Modularized data-driven reconstruction framework for nonideal focal spot effect elimination in computed tomography.

Med Phys 2021 May 23;48(5):2245-2257. Epub 2021 Mar 23.

Department of Radiation Oncology, Stanford University, Stanford, CA, USA.

Purpose: High-performance computed tomography (CT) plays a vital role in clinical decision-making. However, the performance of CT imaging is adversely affected by the nonideal focal spot size of the x-ray source or degraded by an enlarged focal spot size due to aging. In this work, we aim to develop a deep learning-based strategy to mitigate the problem so that high spatial resolution CT images can be obtained even in the case of a nonideal x-ray source.

Methods: To reconstruct high-quality CT images from blurred sinograms via joint image and sinogram learning, a cross-domain hybrid model is formulated via deep learning into a modularized data-driven reconstruction (MDR) framework. The proposed MDR framework comprises several blocks, and all the blocks share the same network architecture and network parameters. In essence, each block utilizes two sub-models to generate an estimated blur kernel and a high-quality CT image simultaneously. In this way, our framework generates not only a final high-quality CT image but also a series of intermediate images with gradually improved anatomical details, enhancing the visual perception for clinicians through the dynamic process. We used simulated training datasets to train our model in an end-to-end manner and tested our model on both simulated and realistic experimental datasets.

Results: On the simulated testing datasets, our approach increases the information fidelity criterion (IFC) by up to 34.2%, the universal quality index (UQI) by up to 20.3%, the signal-to-noise (SNR) by up to 6.7%, and reduces the root mean square error (RMSE) by up to 10.5% as compared with FBP. Compared with the iterative deconvolution method (NSM), MDR increases IFC by up to 24.7%, UQI by up to 16.7%, SNR by up to 6.0%, and reduces RMSE by up to 9.4%. In the modulation transfer function (MTF) experiment, our method improves the MTF by 34.5% and MTF by 18.7% as compared with FBP, Similarly remarkably, our method improves MTF by 14.3% and MTF by 0.9% as compared with NSM. Also, our method shows better imaging results in the edge of bony structures and other tiny structures in the experiments using phantom consisting of ham and a bottle of peanuts.

Conclusions: A modularized data-driven CT reconstruction framework is established to mitigate the blurring effect caused by a nonideal x-ray source with relatively large focal spot. The proposed method enables us to obtain high-resolution images with less ideal x-ray source.
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http://dx.doi.org/10.1002/mp.14785DOI Listing
May 2021

Mitochondria of teleost radial glia: A novel target of neuroendocrine disruption by environmental chemicals?

Comp Biochem Physiol C Toxicol Pharmacol 2021 May 2;243:108995. Epub 2021 Feb 2.

Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida Genetics Institute, Interdisciplinary Program in Biomedical Sciences Neuroscience, College of Veterinary Medicine, University of Florida, Gainesville, FL 32611, USA. Electronic address:

In teleost fish, radial glial cells (RGCs) are progenitor cells for neurons and the major cell type synthesizing neuroestrogens. We hypothesized that chemical exposure impairs mitochondrial bioenergetics of RGCs, which then may lead to downstream consequences for neuroestrogen production. Here we provide proof of concept that mitochondria of RGCs can be perturbed by fungicides. We isolated RGCs from a mixed sex population of goldfish (Carassius auratus) and measured metabolic capacity of primary cells to a model mitotoxin fluazinam, a broad-spectrum fungicide that inhibits mitochondria electron transport chain (or ETC) Complex I. Using immunocytochemistry and real-time PCR, we demonstrate that the goldfish primary cell cultures are highly enriched for glia after multiple passages. Cytotoxicity assays revealed that glia treated with >25 μM fluazinam for 24 and 48-h showed reduced viability. As such, metabolic assays were conducted with non-cytotoxic concentrations (0.25-12.5 μM). Fluazinam did not affect oxygen consumption rates of RGCs at 24 h, but after 48 h, oligomycin induced ATP-linked respiration was decreased by both 6.25 and 12.5 μM fluazinam. Moreover, concentrations as low as 0.25 μM disrupted the mitochondrial membrane potential of RGCs, reflecting strong uncoupling effects of the fungicide on mitochondria. Here we provide proof of concept that mitochondrial bioenergetics of teleostean RGCs can be responsive to agrochemicals. Additional studies are required to address low-dose exposures in vivo and to determine if metabolic disruption impairs neuroendocrine functions of RGCs. We propose this mechanism constitutes a novel aspect of neuroendocrine disruption, significant because dysregulation of neuron-glia communication is expected to contribute to neuroendocrine disruption.
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http://dx.doi.org/10.1016/j.cbpc.2021.108995DOI Listing
May 2021

Multicellular Spheroids as In Vitro Models of Oxygen Depletion During FLASH Irradiation.

Int J Radiat Oncol Biol Phys 2021 Jul 3;110(3):833-844. Epub 2021 Feb 3.

Department of Radiation Oncology, Stanford University, Stanford, California. Electronic address:

Purpose: The differential response of normal and tumor tissues to ultrahigh-dose-rate radiation (FLASH) has raised new hope for treating solid tumors but, to date, the mechanism remains elusive. One leading hypothesis is that FLASH radiochemically depletes oxygen from irradiated tissues faster than it is replenished through diffusion. The purpose of this study was to investigate these effects within hypoxic multicellular tumor spheroids through simulations and experiments.

Methods And Materials: Physicobiological equations were derived to model (1) the diffusion and metabolism of oxygen within spheroids; (2) its depletion through reactions involving radiation-induced radicals; and (3) the increase in radioresistance of spheroids, modeled according to the classical oxygen enhancement ratio and linear-quadratic response. These predictions were then tested experimentally in A549 spheroids exposed to electron irradiation at conventional (0.075 Gy/s) or FLASH (90 Gy/s) dose rates. Clonogenic survival, cell viability, and spheroid growth were scored postradiation. Clonogenic survival of 2 other cell lines was also investigated.

Results: The existence of a hypoxic core in unirradiated tumor spheroids is predicted by simulations and visualized by fluorescence microscopy. Upon FLASH irradiation, this hypoxic core transiently expands, engulfing a large number of well-oxygenated cells. In contrast, oxygen is steadily replenished during slower conventional irradiation. Experimentally, clonogenic survival was around 3-fold higher in FLASH-irradiated spheroids compared with conventional irradiation, but no significant difference was observed for well-oxygenated 2-dimensional cultured cells. This differential survival is consistent with the predictions of the computational model. FLASH irradiation of spheroids resulted in a dose-modifying factor of around 1.3 for doses above 10 Gy.

Conclusions: Tumor spheroids can be used as a model to study FLASH irradiation in vitro. The improved survival of tumor spheroids receiving FLASH radiation confirms that ultrafast radiochemical oxygen depletion and its slow replenishment are critical components of the FLASH effect.
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http://dx.doi.org/10.1016/j.ijrobp.2021.01.050DOI Listing
July 2021

A carrier-free anti-inflammatory platinum (II) self-delivered nanoprodrug for enhanced breast cancer therapy.

J Control Release 2021 Mar 3;331:460-471. Epub 2021 Feb 3.

State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; Prevention and Treatment of High Incidence Diseases in Central Asia, Prevention and Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University, Urumqi, 830054, China; College of Pharmacy, Xinjiang Medical University, Urumqi 830011, China. Electronic address:

Cisplatin is one of the most used first-line anticancer drugs for various solid tumor therapies. However, cisplatin-based chemotherapy can induce tumor cells to secrete excessive prostaglandin E2 (PGE2) catalyzed by cyclooxygenase-2 (COX-2), which, in turn, counteracts its chemotherapeutic effect and further accelerates tumor metastasis. Here, we report a carrier-free self-delivered nanoprodrug based on platinum (II) coordination bonding coupled with tolfenamic acid (Tolf) (named Tolfplatin). Tolfplatin can spontaneously assemble into uniformly sized nanoparticles (NPs) with a high drug-loading capacity. Compared with cisplatin, Tolfplatin NPs can facilitate cellular uptake, significantly decrease PGE2 secretion by COX-2 inhibition, which further downregulate tumorous anti-apoptotic and metastasis-associated proteins, thereby efficiently inducing apoptotic cell death and significantly inhibit tumor metastasis in vitro and in vivo. Therefore, as the carrier-free nanoprodrug, Tolfplatin NPs are promising anti-tumoral agents to inhibit tumor proliferation and metastasis by enriching the function and promoting the anti-tumor activity of cisplatin.
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http://dx.doi.org/10.1016/j.jconrel.2021.01.037DOI Listing
March 2021

Automated contour propagation of the prostate from pCT to CBCT images via deep unsupervised learning.

Med Phys 2021 Apr 1;48(4):1764-1770. Epub 2021 Mar 1.

Department of Radiation Oncology, Stanford University, Stanford, CA, 94305, USA.

Purpose: To develop and evaluate a deep unsupervised learning (DUL) framework based on a regional deformable model for automated prostate contour propagation from planning computed tomography (pCT) to cone-beam CT (CBCT).

Methods: We introduce a DUL model to map the prostate contour from pCT to on-treatment CBCT. The DUL framework used a regional deformable model via narrow-band mapping to augment the conventional strategy. Two hundred and fifty-one anonymized CBCT images from prostate cancer patients were retrospectively selected and divided into three sets: 180 were used for training, 12 for validation, and 59 for testing. The testing dataset was divided into two groups. Group 1 contained 50 CBCT volumes, with one physician-generated prostate contour on CBCT image. Group 2 contained nine CBCT images, each including prostate contours delineated by four independent physicians and a consensus contour generated using the STAPLE method. Results were compared between the proposed DUL and physician-generated contours through the Dice similarity coefficients (DSCs), the Hausdorff distances, and the distances of the center-of-mass.

Results: The average DSCs between DUL-based prostate contours and reference contours for test data in group 1 and group 2 consensus were 0.83 ± 0.04, and 0.85 ± 0.04, respectively. Correspondingly, the mean center-of-mass distances were 3.52 mm ± 1.15 mm, and 2.98 mm ± 1.42 mm, respectively.

Conclusions: This novel DUL technique can automatically propagate the contour of the prostate from pCT to CBCT. The proposed method shows that highly accurate contour propagation for CBCT-guided adaptive radiotherapy is achievable via the deep learning technique.
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http://dx.doi.org/10.1002/mp.14755DOI Listing
April 2021

Magnetic FeO/attapulgite hybrids for Cd(II) adsorption: Performance, mechanism and recovery.

J Hazard Mater 2021 06 26;412:125237. Epub 2021 Jan 26.

School of Chemistry and Environmental Engineering & Hubei Engineering Technology Research Center for Chemical Industry Pollution Control, Wuhan Institute of Technology, Wuhan 430205, China. Electronic address:

Herein, a FeO decorated attapulgite adsorbent (FA) is fabricated for the removal of Cd(II) from wastewater, and subsequently a feasible strategy for converting the saturated waste adsorbent to CdS/FA photocatalyst is reported. Owing to the in situ growth of FeO on the attapulgite (ATP), the FA adsorbents exhibit enlarged surface area and increased adsorption sites. More importantly, the strong interaction between FeO and ATP leads to changes of coordination environment around the O‒Fe‒O bond with the ATP. Based on the results of density functional theory calculations, the electrons are more readily transferred from Fe to O, and the hanging O atoms with more electronegativity act as the efficient adsorption sites for Cd(II), efficiently improving the adsorption performance of the FeO phases. Furthermore, the waste FA adsorbent could be conveniently separated from the treated water by magnets and converted to CdS/FA photocatalyst, which exhibits satisfying degradation efficiency for tetracycline with low concentration. This work provides a potential strategy to optimize the ATP-based materials for heavy ions adsorption and reutilize the waste adsorbents.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125237DOI Listing
June 2021

Pareto Optimal Projection Search (POPS): Automated Radiation Therapy Treatment Planning by Direct Search of the Pareto Surface.

IEEE Trans Biomed Eng 2021 Feb 1;PP. Epub 2021 Feb 1.

Objective: Radiation therapy treatment planning is a time-consuming, iterative process with potentially high inter-planner variability. Fully automated treatment planning processes could reduce a planner's active treatment planning time and remove inter-planner variability, with the potential to tremendously improve patient turnover and quality of care. In developing fully automated algorithms for treatment planning, we have two main objectives: to produce plans that are 1) Pareto optimal and 2) clinically acceptable. Here, we propose the Pareto optimal projection search (POPS) algorithm, which provides a general framework for directly searching the Pareto front.

Methods: Our POPS algorithm is a novel automated planning method that combines two main search processes: 1) gradient-free search in the decision variable space and 2) projection of decision variables to the Pareto front using the bisection method. We demonstrate the performance of POPS by comparing with clinical treatment plans. As one possible quantitative measure of treatment plan quality, we construct a clinical acceptability scoring function (SF) modified from the previously developed general evaluation metric (GEM).

Results: On a dataset of 21 prostate cases collected as part of clinical workflow, our proposed POPS algorithm produces Pareto optimal plans that are clinically acceptable in regards to dose conformity, dose homogeneity, and sparing of organs-at-risk.

Conclusion: Our proposed POPS algorithm provides a general framework for fully automated treatment planning that achieves clinically acceptable dosimetric quality without requiring active planning from human planners.

Significance: Our fully automated POPS algorithm addresses many key limitations of other automated planning approaches, and we anticipate that it will substantially improve treatment planning workflow.
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http://dx.doi.org/10.1109/TBME.2021.3055822DOI Listing
February 2021

Morphological Characteristics of Eroded Plaques with Noncritical Coronary Stenosis: An Optical Coherence Tomography Study.

J Atheroscler Thromb 2021 Jan 15. Epub 2021 Jan 15.

Department of Cardiology, The 2nd Affiliated Hospital of Harbin Medical University; The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education.

Aims: Recent studies suggested plaque erosion with noncritical stenosis could be treated distinctly from that with critical stenosis, but their morphological features remained largely unknown. The present study aimed to investigate morphological features of eroded plaques with different lumen stenosis using optical coherence tomography (OCT).

Methods: A total of 348 ST-segment elevated myocardial infarction patients with culprit OCT-defined plaque erosion (OCT-erosion) were analyzed. Based on the severity of lumen area stenosis, all patients with OCT-erosions were divided into the following three groups: Group A (area stenosis <50%, n=50); Group B (50% ≤area stenosis <75%, n=146); Group C (area stenosis ≥ 75%, n=152).

Results: Compared with patients in Groups A and B, patients in Group C were older (p=0.008) and had higher prevalence of hypertension (p=0.029). Angiographic analysis showed that 72.0% of the eroded plaques in Group A were located in the left anterior descending artery, followed by 67.8% in Group B, and 53.9% in Group C (p=0.039). OCT analysis showed that Group A had the highest prevalence of fibrous plaques (p<0.001) and nearby bifurcation (p=0.036), but the lowest prevalence of lipid-rich plaques (p<0.001), macrophage accumulation (p<0.001), microvessels (p=0.009), cholesterol crystals (p<0.001), and calcification (p=0.023). Multivariable regression analysis showed fibrous plaque (odds ratio [OR]: 3.014, 95% confidence interval [CI]: 1.932-4.702, p<0.001) and nearby bifurcation (OR: 1.750, 95% CI: 1.109-2.761, p=0.016) were independently associated with OCT-erosion with an area stenosis of <75%.

Conclusions: More than half of OCT-erosions presented with <75% area stenosis, having distinct morphological features from those of OCT-erosions with critical stenosis. Fibrous plaque and nearby bifurcation were independently associated with noncritically stenotic OCT-erosion, suggesting that eroded plaques might need individualized treatment.
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http://dx.doi.org/10.5551/jat.60301DOI Listing
January 2021