Publications by authors named "Xiaofeng Yang"

541 Publications

A rapid preliminary prediction model for intestinal necrosis in acute mesenteric ischemia: a retrospective study.

BMC Gastroenterol 2021 Apr 7;21(1):154. Epub 2021 Apr 7.

Emergency and Trauma Center, The International Medical Center, The First Affiliated Hospital, Zhejiang University School of Medicine, 1367 West Wenyi Rd.Zhejiang Province, Hangzhou, 310058, China.

Background: Acute mesenteric ischemia (AMI) is a life-threatening condition. However, there is no accurate method to predict intestinal necrosis in AMI patients that may facilitate early surgical intervention. This study thus aimed to explore a simple and accurate model to predict intestinal necrosis in patients with AMI.

Methods: A single-center retrospective study was performed on the data of 132 AMI patients treated between October 2011 and June 2020. The patients were divided into the intestinal necrosis and non-intestinal necrosis groups. The clinical characteristics and laboratory data were analyzed by univariate analysis, and the variables with statistical significance were further analyzed by multivariate logistic regression analysis. The independent predictors of intestinal necrosis were determined and a logistic prediction model was established. Finally, the accuracy, sensitivity, and specificity of the model in predicting intestinal necrosis were evaluated.

Results: Univariate analysis showed that white blood cell (WBC) count, blood urea nitrogen (BUN) level, neutrophil ratio, prothrombin time (PT), and LnD-dimer were associated with intestinal necrosis. According to logistic regression multivariate analysis, WBC count, BUN level and LnD-dimer were independent predictors of intestinal necrosis. These parameters were used to establish a clinical prediction model of intestinal necrosis (CPMIN) as follows: model score = 0.349 × BUN (mmol/L) + 0.109 × WBC × 10 (10/L) + 0.394 × LnD - Dimer (ug/L) - 7.883. The area under the receiver operating characteristics (ROC) curve of the model was 0.889 (95% confidence interval: 0.833-0.944). Model scores greater than - 0.1992 predicted the onset of intestinal necrosis. The accuracy, specificity, and sensitivity of the model were 82.6%, 78.2%, and 88.3%, respectively. The proportion of intestinal necrosis in the high-risk patient group (CPMIN score ≥ - 0.1992) was much greater than that in the low-risk patient group (CPMIN score < - 0.1992; 82.7% vs. 15.0%, p < 0.001).

Conclusion: The CPMIN can effectively predict intestinal necrosis and guide early surgical intervention to improve patient prognosis. Patients with AMI who are classified as high-risk should be promptly treated with surgery to avoid the potential complications caused by delayed operation. Patients classified as low-risk group can receive non-surgical treatment. This model may help to lower the morbidity and mortality from AMI. However, this model's accuracy should be validated by larger sample size studies in the future.
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http://dx.doi.org/10.1186/s12876-021-01746-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8028195PMC
April 2021

Tumor Resection, Optical Molecular Imaging, and the Potential Synergy of the Combination of the Two Techniques in Bladder Cancer.

Front Oncol 2021 16;11:638083. Epub 2021 Mar 16.

First Clinical Medical College, Shanxi Medical University, Taiyuan, China.

Although transurethral resection of bladder tumor is the golden standard for the treatment of non-muscle invasive bladder cancer, this surgical procedure still has some serious drawbacks. For example, piecemeal resection of tumor tissue results in exfoliated tumor cells dissemination and implantation, and fragmented tumor specimens make it difficult for pathologists to accurately assess the pathological stage and histologic grade. En bloc tumor resection follows the basic principle of oncological surgery and provides an intact tumor specimen containing detrusor muscle for pathologists to make accurate histopathological assessment. However, there is no robust clinical evidence that en bloc tumor resection is superior to conventional resection in terms of oncological outcomes. Considering the high recurrence rate, small or occult tumor lesions may be overlooked and incomplete tumor resection may occur during white light cystoscopy-assisted transurethral resection. Molecular fluorescent tracers have the ability to bind tumor cells with high sensitivity and specificity. Optical molecular imaging mediated by it can detect small or occult malignant lesions while minimizing the occurrence of false-positive results. Meanwhile, optical molecular imaging can provide dynamic and real-time image guidance in the surgical procedure, which helps urologists to accurately determine the boundary and depth of tumor invasion, so as to perform complete and high-quality transurethral tumor resection. Integrating the advantages of these two technologies, optical molecular imaging-assisted en bloc tumor resection shows the potential to improve the positive detection rate of small or occult tumor lesions and the quality of transurethral resection, resulting in high recurrence-free and progression-free survival rates.
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http://dx.doi.org/10.3389/fonc.2021.638083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008058PMC
March 2021

Male pelvic CT multi-organ segmentation using synthetic MRI-aided dual pyramid networks.

Phys Med Biol 2021 Apr 16;66(8). Epub 2021 Apr 16.

Department of Radiation Oncology and Winship Cancer Institute, Emory University, Atlanta, GA 30322, United States of America.

The delineation of the prostate and organs-at-risk (OARs) is fundamental to prostate radiation treatment planning, but is currently labor-intensive and observer-dependent. We aimed to develop an automated computed tomography (CT)-based multi-organ (bladder, prostate, rectum, left and right femoral heads (RFHs)) segmentation method for prostate radiation therapy treatment planning. The proposed method uses synthetic MRIs (sMRIs) to offer superior soft-tissue information for male pelvic CT images. Cycle-consistent adversarial networks (CycleGAN) were used to generate CT-based sMRIs. Dual pyramid networks (DPNs) extracted features from both CTs and sMRIs. A deep attention strategy was integrated into the DPNs to select the most relevant features from both CTs and sMRIs to identify organ boundaries. The CT-based sMRI generated from our previously trained CycleGAN and its corresponding CT images were inputted to the proposed DPNs to provide complementary information for pelvic multi-organ segmentation. The proposed method was trained and evaluated using datasets from 140 patients with prostate cancer, and were then compared against state-of-art methods. The Dice similarity coefficients and mean surface distances between our results and ground truth were 0.95 ± 0.05, 1.16 ± 0.70 mm; 0.88 ± 0.08, 1.64 ± 1.26 mm; 0.90 ± 0.04, 1.27 ± 0.48 mm; 0.95 ± 0.04, 1.08 ± 1.29 mm; and 0.95 ± 0.04, 1.11 ± 1.49 mm for bladder, prostate, rectum, left and RFHs, respectively. Mean center of mass distances was within 3 mm for all organs. Our results performed significantly better than those of competing methods in most evaluation metrics. We demonstrated the feasibility of sMRI-aided DPNs for multi-organ segmentation on pelvic CT images, and its superiority over other networks. The proposed method could be used in routine prostate cancer radiotherapy treatment planning to rapidly segment the prostate and standard OARs.
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http://dx.doi.org/10.1088/1361-6560/abf2f9DOI Listing
April 2021

A Genetic Model Reveals Biological Features of Neonatal CD4 Helper Cells Undergone Homeostasis in Mice.

Front Cell Dev Biol 2021 11;9:659744. Epub 2021 Mar 11.

Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, China.

CD4 T cells are essential for regulating effective immune response to pathogens and immune balance. Recent studies have demonstrated the unique features of T cells in neonate mice, such as more sensitive to antigen response and preference toward T helper 2 (Th2) response and regulatory T cells (Tregs) differentiation. However, the biological characteristics of neonatal age-derived CD4 T cells following homeostasis remain unclear. Here we utilized a lineage tracing model of δ to mark neonatal- and adult-derived CD4 T cells followed by a combination analysis of activation, proliferation, survival, and differentiation. Our results showed that neonatal CD4 T cells had higher capacity of activation, proliferation, apoptosis, and differentiation toward Th2 and T helper 17 (Th17) lineages, accompanied by a reduced potential for T helper 1 (Th1), T helper 9 (Th9), and Treg lineages. In contrast, tracked neonatal CD4 T cells exhibited similar characters of above-mentioned of tracked adult cells in adult mice. Therefore, our data support a natural requirement for CD4 T cells to acquire fully-equipped functional potentials of adult cells.
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http://dx.doi.org/10.3389/fcell.2021.659744DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7991801PMC
March 2021

Overnight Continuous Saline Bladder Irrigation After Resection of Bladder Tumor Does Not Improve Oncological Outcomes in Patients Who Have Received Intravesical Chemotherapy.

Front Oncol 2021 10;11:638065. Epub 2021 Mar 10.

First Clinical Medical College, Shanxi Medical University, Taiyuan, China.

Objective: To evaluate the safety and efficacy of overnight continuous saline bladder irrigation (CSBI) for patients who have received thulium laser resection of bladder tumor (TmLRBT) combined with immediate intravesical chemotherapy previously.

Methods: From October 2014 to June 2018, 235 patients with newly diagnosed non-muscle invasive bladder cancer (NMIBC) were included in this retrospective study. All patients received intravesical instillation of pirarubicin immediately after TmLRBT. The patients were divided into two groups according to the duration of postoperative bladder irrigation with normal saline. After immediate intravesical chemotherapy, patients in group 1 received overnight CSBI, while patients in group 2 did not receive overnight CSBI. Data on the time of initial tumor recurrence, recurrence-free survival (RFS) and progression-free survival (PFS) rates, and perioperative complications were collected and analyzed.

Results: Of 235 included patients (129 in group 1 and 106 in group 2), the median follow-up periods were 42 and 38 months, respectively. There were no significant differences in patients' baseline characteristics between the two groups. The RFS rates of patients in group 1 were 90.7, 82.7, and 76.8% at the end of the first, third, and fifth years, while the corresponding RFS rates of patients in group 2 were 87.7, 78.9, and 73.3%, respectively. Four patients in group 1 and five patients in group 2 experienced tumor progression. No significant differences between the two groups were observed in the time of initial tumor recurrence, RFS, and PFS rates. Only Grade I complications occurred in the two groups, and no significant difference was reached between the two groups.

Conclusions: For patients with NMIBC who have previously received TmLRBT combined with immediate intravesical chemotherapy, overnight CSBI may not improve oncological outcomes and reduce perioperative complications.
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http://dx.doi.org/10.3389/fonc.2021.638065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988089PMC
March 2021

cyst fluid suppresses inflammatory responses by inhibiting TRAF6 signalling in macrophages.

Parasitology 2021 Mar 29:1-8. Epub 2021 Mar 29.

Department of Immunology, Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, Xinjiang, China.

Echinococcus granulosus sensu lato has complex defence mechanisms that protect it from the anti-parasitic immune response for long periods. Echinococcus granulosus cyst fluid (EgCF) is involved in the immune escape. Nevertheless, whether and how EgCF modulates the inflammatory response in macrophages remains poorly understood. Here, real-time polymerase chain reaction and enzyme-linked immunosorbent assay revealed that EgCF could markedly attenuate the lipopolysaccharide (LPS)-induced production of pro-inflammatory factors including tumour necrosis factor-α, interleukin (IL)-12 and IL-6 but increase the expression of IL-10 at mRNA and protein levels in mouse peritoneal macrophages and RAW 264.7 cells. Mechanically, western blotting and immunofluorescence assay showed that EgCF abolished the activation of nuclear factor (NF)-κB p65, p38 mitogen-activated protein kinase (MAPK) and ERK1/2 signalling pathways by LPS stimulation in mouse macrophages. EgCF's anti-inflammatory role was at least partly contributed by promoting proteasomal degradation of the critical adaptor TRAF6. Moreover, the EgCF-promoted anti-inflammatory response and TRAF6 proteasomal degradation were conserved in human THP-1 macrophages. These findings collectively reveal a novel mechanism by which EgCF suppresses inflammatory responses by inhibiting TRAF6 and the downstream activation of NF-κB and MAPK signalling in both human and mouse macrophages, providing new insights into the molecular mechanisms underlying the E. granulosus-induced immune evasion.
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http://dx.doi.org/10.1017/S0031182021000548DOI Listing
March 2021

Med1 controls CD8 T cell maintenance through IL-7R-mediated cell survival signalling.

J Cell Mol Med 2021 Mar 17. Epub 2021 Mar 17.

Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, China.

Under steady-state conditions, the pool size of peripheral CD8 T cells is maintained through turnover and survival. Beyond TCR and IL-7R signals, the underlying mechanisms are less well understood. In the present study, we found a significant reduction of CD8 T cell proportion in spleens but not in thymi of mice with T cell-specific deletion of Mediator Subunit 1 (Med1). A competitive transfer of wild-type (WT) and Med1-deficient CD8 T cells reproduced the phenotype in the same recipients and confirmed intrinsic role of Med1. Furthermore, we observed a comparable degree of migration and proliferation but a significant increase of cell death in Med1-deficient CD8 T cells compared with WT counterparts. Finally, Med1-deficient CD8 T cells exhibited a decreased expression of interleukin-7 receptor α (IL-7Rα), down-regulation of phosphorylated-STAT5 (pSTAT5) and Bim up-regulation. Collectively, our study reveals a novel role of Med1 in the maintenance of CD8 T cells through IL-7Rα/STAT5 pathway-mediated cell survival.
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http://dx.doi.org/10.1111/jcmm.16465DOI Listing
March 2021

Optimal Algorithms for Ranked Enumeration of Answers to Full Conjunctive Queries.

Proceedings VLDB Endowment 2020 May;13(9):1582-1597

VMware, Palo Alto, CA, USA.

We study ranked enumeration of join-query results according to very general orders defined by selective dioids. Our main contribution is a framework for ranked enumeration over a class of dynamic programming problems that generalizes seemingly different problems that had been studied in isolation. To this end, we extend classic algorithms that find the -shortest paths in a weighted graph. For full conjunctive queries, including cyclic ones, our approach is optimal in terms of the time to return the top result and the delay between results. These optimality properties are derived for the widely used notion of data complexity, which treats query size as a constant. By performing a careful cost analysis, we are able to uncover a previously unknown trade-off between two incomparable enumeration approaches: one has lower complexity when the number of returned results is small, the other when the number is very large. We theoretically and empirically demonstrate the superiority of our techniques over batch algorithms, which produce the full result and then sort it. Our technique is not only faster for returning the first few results, but on some inputs beats the batch algorithm even when all results are produced.
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http://dx.doi.org/10.14778/3397230.3397250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955775PMC
May 2020

Immunological Feature and Transcriptional Signaling of Ly6C Monocyte Subsets From Transcriptome Analysis in Control and Hyperhomocysteinemic Mice.

Front Immunol 2021 25;12:632333. Epub 2021 Feb 25.

Department of Pharmacology, Center for Metabolic Disease Research, Lewis Kats School of Medicine, Temple University, Philadelphia, PA, United States.

Background: Murine monocytes (MC) are classified into Ly6C and Ly6C MC. Ly6C MC is the pro-inflammatory subset and the counterpart of human CD14CD16 intermediate MC which contributes to systemic and tissue inflammation in various metabolic disorders, including hyperhomocysteinemia (HHcy). This study aims to explore molecule signaling mediating MC subset differentiation in HHcy and control mice.

Methods: RNA-seq was performed in blood Ly6C and Ly6C MC sorted by flow cytometry from control and HHcy cystathionine β-synthase gene-deficient () mice. Transcriptome data were analyzed by comparing Ly6C vs. Ly6C in control mice, Ly6C vs. Ly6C in mice, Ly6C vs. control Ly6C MC and Ly6C vs. control Ly6C MC by using intensive bioinformatic strategies. Significantly differentially expressed (SDE) immunological genes and transcription factor (TF) were selected for functional pathways and transcriptional signaling identification.

Results: A total of 7,928 SDE genes and 46 canonical pathways derived from it were identified. Ly6C MC exhibited activated neutrophil degranulation, lysosome, cytokine production/receptor interaction and myeloid cell activation pathways, and Ly6C MC presented features of lymphocyte immunity pathways in both mice. Twenty-four potential transcriptional regulatory pathways were identified based on SDE TFs matched with their corresponding SDE immunological genes. Ly6C MC presented downregulated co-stimulatory receptors (CD2, GITR, and TIM1) which direct immune cell proliferation, and upregulated co-stimulatory ligands (LIGHT and SEMA4A) which trigger antigen priming and differentiation. Ly6C MC expressed higher levels of macrophage (MΦ) markers, whereas, Ly6C MC highly expressed lymphocyte markers in both mice. HHcy in mice reinforced inflammatory features in Ly6C MC by upregulating inflammatory TFs ( and ) and strengthened lymphocytes functional adaptation in Ly6C MC by increased expression of CD3, DR3, ICOS, and . Finally, we established 3 groups of transcriptional models to describe Ly6C to Ly6C MC subset differentiation, immune checkpoint regulation, Ly6C MC to MΦ subset differentiation and Ly6C MC to lymphocyte functional adaptation.

Conclusions: Ly6C MC displayed enriched inflammatory pathways and favored to be differentiated into MΦ. Ly6C MC manifested activated T-cell signaling pathways and potentially can adapt the function of lymphocytes. HHcy reinforced inflammatory feature in Ly6C MC and strengthened lymphocytes functional adaptation in Ly6C MC.
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http://dx.doi.org/10.3389/fimmu.2021.632333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947624PMC
February 2021

Safety and efficacy of long-term mild hypothermia for severe traumatic brain injury with refractory intracranial hypertension (LTH-1): A multicenter randomized controlled trial.

EClinicalMedicine 2021 Feb 28;32:100732. Epub 2021 Jan 28.

Head Trauma Center, Department of Neurosurgery, Renji Hospital, Shanghai Jiao Tong University/School of Medicine, Shanghai Institute of Head Trauma, Shanghai, China.

Background: Therapeutic hypothermia may need prolonged duration for the patients with severe traumatic brain injury (sTBI).

Methods: The Long-Term Hypothermia trial was a prospective, multicenter, randomized, controlled clinical trial to examine the safety and efficacy in adults with sTBI. Eligible patients were 18-65, Glasgow Coma Scale score at 4 to 8, and initial intracranial pressure (ICP) ≥ 25 mm Hg, randomly assigned to the long-term mild hypothermia group (34-35 °C for 5 days) or normothermia group at 37 °C. The primary outcome was the Glasgow outcome scale (GOS) at 6 months. Secondary outcomes included ICP control, complications and laboratory findings, the length of ICU and hospital stay, and GOS at 6 months in patients with initial ICP ≥ 30 mm Hg. This trial is registered with ClinicalTrials.gov, NCT01886222.

Findings: 302 patients were enrolled from June 25, 2013, to December 31, 2018, with 6 months follow-up in 14 hospitals, 156 in hypothermia group and 146 in normothermia group. There was no difference in favorable outcome (OR 1·55, 95%CI 0·91-2·64;  = 0·105) and in mortality ( = 0·111) between groups. In patients with an initial ICP ≥ 30 mm Hg, hypothermic treatment significantly increased favorable outcome over normothermia group (60·82%, 42·71%, respectively; OR 1·861, 95%CI 1·031-3·361;  = 0·039). Long-term mild hypothermia did not increase the incidences of complications.

Interpretation: Long-term mild hypothermia did not improve the neurological outcomes. However, it may be a potential option in sTBI patients with initial ICP ≥ 30 mm Hg.

Funding: : Shanghai municipal government and Shanghai Jiao Tong University/School of Medicine.
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http://dx.doi.org/10.1016/j.eclinm.2021.100732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910713PMC
February 2021

FAST1 Predicts Poor Survival of Renal Carcinoma and Promotes Its Progression Through the TGF-β/Smad Pathway.

Onco Targets Ther 2021 26;14:1487-1499. Epub 2021 Feb 26.

Department of Urology, Zaozhuang Municipal Hospital, Zaozhuang, 277100, Shandong, People's Republic of China.

Purpose: Renal carcinoma (RC) originates in the renal tubular epithelial system, among which renal cell carcinoma (RCC) is the most frequent one. The forkhead activin signal transducer 1 (FAST1) has been shown to interfere with tumor progression as an oncogene, while its role in RC is limited. Therefore, this paper explored the prognostic significance, specific effects, and related mechanisms of FAST1 on RC.

Patients And Methods: Cell colony formation assay, cell counting kit-8 (CCK8) assay, flow cytometry and Transwell assay were used to test cell proliferation, viability, apoptosis, migration and invasion, respectively. Western blot (WB) was employed to determine the protein level of FAST1.

Results: Our study confirmed that FAST1 was up-regulated in RC tissues and cell lines, and its overexpression often represented a poor prognosis of RC patients. Meanwhile, the in vitro experiments showed that overexpressing FAST1 facilitated RC cell viability, proliferation, migration, invasion and epithelial-mesenchymal transition (EMT), and repressed cell apoptosis. In addition, the in vivo experiments illustrated that the up-regulation of FAST1 strengthened tumor growth. On the contrary, knocking down FAST1 had the opposite effects. Mechanistically, The TGF-β/Smad pathway contributed to RC evolvement and was activated by FAST1 both in vitro and in vivo.

Conclusion: This article suggests that FAST1 exerts a carcinogenic role in RC by regulating the TGF-β/Smad signaling.
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http://dx.doi.org/10.2147/OTT.S288847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926040PMC
February 2021

Traumatic Brain Injury Induces Gastrointestinal Dysfunction and Dysbiosis of Gut Microbiota Accompanied by Alterations of Bile Acid Profile.

J Neurotrauma 2021 Apr 14. Epub 2021 Apr 14.

Emergency and Trauma Center and The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.

Gastrointestinal dysfunction is a common peripheral organ complication after traumatic brain injury (TBI), yet the underlying mechanism remains unknown. TBI has been demonstrated to cause gut microbiota dysbiosis in animal models, although the impacts of gut microbiota dysbiosis on gastrointestinal dysfunction were not examined. Bile acids are key metabolites between gut microbiota and host interactions. Therefore, the aim of this study was to investigate the mechanistic links between them by detecting the alterations of gut microbiota and bile acid profile after TBI. For that, we established TBI in mice using a lateral fluid percussion injury model. Gut microbiota was examined by 16S rRNA sequencing, and bile acids were profiled by ultra-performance liquid chromatography-tandem mass spectrometry. Our results showed that TBI caused intestinal inflammation and gut barrier impairment. Alterations of gut microbiota and bile acid profile were observed. The diversity of gut microbiota experienced a time dependent change from 1 h to 7 days post-injury. Levels of bile acids in feces and plasma were decreased after TBI, and the decrease was more significant in secondary bile acids, which may contribute to intestinal inflammation. Specific bacterial taxa such as Staphylococcus and Lachnospiraceae that may contribute to the bile acid metabolic changes were identifed. In conclusion, our study suggested that TBI-induced gut microbiota dysbiosis may contribute to gastrointestinal dysfunction via altering bile acid profile. Gut microbiota may be a potential treatment target for TBI-induced gastrointestinal dysfunction.
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http://dx.doi.org/10.1089/neu.2020.7526DOI Listing
April 2021

Engineering of the sRNA DsrA together with the sRNA chaperone Hfq enhances the acid tolerance of .

Appl Environ Microbiol 2021 Mar 5. Epub 2021 Mar 5.

School of Biology and Biological Engineering, South China University of Technology, Guangzhou, Guangdong 510006, China

Acid tolerance of microorganism is a desirable phenotype for many industrial fermentation applications. In , the stress response sigma factor RpoS is a promising target for engineering acid tolerant phenotypes. However, the simple overexpression of RpoS alone is insufficient to confer these phenotypes. In this study, we showed that the simultaneous overexpression of the noncoding small RNA (sRNA) DsrA and the sRNA chaperone Hfq, which act as RpoS activators, significantly increased the acid tolerance, in terms of cell growth under modest acidic pH, as well as cell survival upon extreme acid shock. Directed evolution of the DsrA-Hfq module further improved the acid tolerance, with the best mutants showing a 51%-72% increase in growth performance at pH 4.5 compared with the starting strain MG1655. Further analyses found that the improved acid tolerance of these DsrA-Hfq strains coincided with activation of genes associated with the proton-consuming acid resistance system 2 (AR2), protein chaperone HdeB, and reactive oxygen species (ROS) removal in the exponential phase. This study illustrated that the fine-tuning of sRNAs and their chaperones, can be a novel strategy for improving the acid tolerance of Many of the traditional studies on bacterial acid tolerance generally focused on improving cell survival under extreme pH conditions, but cell growth under less harsh acidic conditions is more relevant to industrial applications. Under normal conditions, the general stress response sigma factor RpoS is maintained at low levels in the growth phase through a number of mechanisms. This study showed that RpoS can be activated prior to the stationary phase via engineering its activators, the sRNA DsrA and the sRNA chaperone Hfq, resulting in significantly improved cell growth at modest acidic pH. This work suggests that the sigma factors and likely other transcription factors, can be re-tuned or re-timed by manipulating the respective regulatory sRNAs along with the sufficient supply of the respective sRNA chaperones (, Hfq). This provides a novel avenue for strain engineering of microbes.
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http://dx.doi.org/10.1128/AEM.02923-20DOI Listing
March 2021

Echocardiographic image multi-structure segmentation using Cardiac-SegNet.

Med Phys 2021 Mar 2. Epub 2021 Mar 2.

Department of Radiation Oncology and Winship Cancer Institute, Emory University, Atlanta, GA, 30322, USA.

Purpose: Cardiac boundary segmentation of echocardiographic images is important for cardiac function assessment and disease diagnosis. However, it is challenging to segment cardiac ventricles due to the low contrast-to-noise ratio and speckle noise of the echocardiographic images. Manual segmentation is subject to interobserver variability and is too slow for real-time image-guided interventions. We aim to develop a deep learning-based method for automated multi-structure segmentation of echocardiographic images.

Methods: We developed an anchor-free mask convolutional neural network (CNN), termed Cardiac-SegNet, which consists of three subnetworks, that is, a backbone, a fully convolutional one-state object detector (FCOS) head, and a mask head. The backbone extracts multi-level and multi-scale features from endocardium image. The FOCS head utilizes these features to detect and label the region-of-interests (ROIs) of the segmentation targets. Unlike the traditional mask regional CNN (Mask R-CNN) method, the FCOS head is anchor-free and can model the spatial relationship of the targets. The mask head utilizes a spatial attention strategy, which allows the network to highlight salient features to perform segmentation on each detected ROI. For evaluation, we investigated 450 patient datasets by a five-fold cross-validation and a hold-out test. The endocardium (LV ) and epicardium (LV ) of the left ventricle and left atrium (LA) were segmented and compared with manual contours using the Dice similarity coefficient (DSC), Hausdorff distance (HD), mean absolute distance (MAD), and center-of-mass distance (CMD).

Results: Compared to U-Net and Mask R-CNN, our method achieved higher segmentation accuracy and fewer erroneous speckles. When our method was evaluated on a separate hold-out dataset at the end diastole (ED) and the end systole (ES) phases, the average DSC were 0.952 and 0.939 at ED and ES for the LV , 0.965 and 0.959 at ED and ES for the LV , and 0.924 and 0.926 at ED and ES for the LA. For patients with a typical image size of 549 × 788 pixels, the proposed method can perform the segmentation within 0.5 s.

Conclusion: We proposed a fast and accurate method to segment echocardiographic images using an anchor-free mask CNN.
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http://dx.doi.org/10.1002/mp.14818DOI Listing
March 2021

Automatic delineation of cardiac substructures using a region-based fully convolutional network.

Med Phys 2021 Mar 2. Epub 2021 Mar 2.

Department of Radiation Oncology and Winship Cancer Institute, Emory University, Atlanta, GA, USA.

Purpose: Radiation dose to specific cardiac substructures, such as the atria and ventricles, has been linked to post-treatment toxicity and has shown to be more predictive of these toxicities than dose to the whole heart. A deep learning-based algorithm for automatic generation of these contours is proposed to aid in either retrospective or prospective dosimetric studies to better understand the relationship between radiation dose and toxicities.

Methods: The proposed method uses a mask-scoring regional convolutional neural network (RCNN) which consists of five major subnetworks: backbone, regional proposal network (RPN), RCNN head, mask head, and mask-scoring head. Multiscale feature maps are learned from computed tomography (CT) via the backbone network. The RPN utilizes these feature maps to detect the location and region-of-interest (ROI) of all substructures, and the final three subnetworks work in series to extract structural information from these ROIs. The network is trained using 55 patient CT datasets, with 22 patients having contrast scans. Threefold cross validation (CV) is used for evaluation on 45 datasets, and a separate cohort of 10 patients are used for holdout evaluation. The proposed method is compared to a 3D UNet.

Results: The proposed method produces contours that are qualitatively similar to the ground truth contours. Quantitatively, the proposed method achieved average Dice score coefficients (DSCs) for the whole heart, chambers, great vessels, coronary arteries, the valves of the heart of 0.96, 0.94, 0.93, 0.66, and 0.77 respectively, outperforming the 3D UNet, which achieved DSCs of 0.92, 0.87, 0.88, 0.48, and 0.59 for the corresponding substructure groups. Mean surface distances (MSDs) between substructures segmented by the proposed method and the ground truth were <2 mm except for the left anterior descending coronary artery and the mitral and tricuspid valves, and <5 mm for all substructures. When dividing results into noncontrast and contrast datasets, the model performed statistically significantly better in terms of DSC, MSD, centroid mean distance (CMD), and volume difference for the chambers and whole heart with contrast. Notably, the presence of contrast did not statistically significantly affect coronary artery segmentation DSC or MSD. After network training, all substructures and the whole heart can be segmented on new datasets in less than 5 s.

Conclusions: A deep learning network was trained for automatic delineation of cardiac substructures based on CT alone. The proposed method can be used as a tool to investigate the relationship between cardiac substructure dose and treatment toxicities.
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http://dx.doi.org/10.1002/mp.14810DOI Listing
March 2021

[Corrigendum] Silencing of type Iγ phosphatidylinositol phosphate kinase suppresses ovarian cancer cell proliferation, migration and invasion.

Oncol Rep 2021 Apr 18;45(4). Epub 2021 Feb 18.

Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55901, USA.

Subsequently to the publication of the above paper, the authors have drawn to our attention that the middle panel in Fig. 3B, representing the migration of PIPKIγ‑depleted cells (PIPKIγ‑1), was inadvertently mixed up with the left panel of control cells (siRNA Ctrl). The results presented in Fig. 3D, however, were quantified based on the original images from three independent experiments, each containing five randomly picked micro-scopic fields. The authors were able to re‑examine the original data files and retrieve the correct data panels. The revised version of Fig. 3, featuring the correct data for the 'PIPKIγ‑1' panel in Fig. 3B, is shown below. Note that the error made inadvertently with the selection of the representative image for PIPKIγ‑1 in Fig. 3B did not affect the overall conclusions reported for this experiment. The authors are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this Corrigendum, and apologize to the readership for any inconvenience caused. [the original article was published in Oncology Reports 38: 253‑262, 2017; DOI: 10.3892/or.2017.5670].
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http://dx.doi.org/10.3892/or.2021.7982DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934217PMC
April 2021

Age-Related Gene Alteration in Naïve and Memory T cells Using Precise Age-Tracking Model.

Front Cell Dev Biol 2020 11;8:624380. Epub 2021 Feb 11.

Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, China.

In aged individuals, age-related changes in immune cells, especially T cell deficiency, are associated with an increased incidence of infection, tumor, and autoimmune disease, as well as an impaired response to vaccination. However, the features of gene expression levels in aged T cells are still unknown. Our previous study successfully tracked aged T cells generated from one wave of developing thymocytes of young age by a lineage-specific and inducible Cre-controlled reporter (δ mouse strain). In this study, we utilized this model and genome-wide transcriptomic analysis to examine changes in gene expression in aged naïve and memory T cell populations during the aging process. We identified profound gene alterations in aged CD4 and CD8 T cells. Both aged CD4 and CD8 naïve T cells showed significantly decreased organelle function. Importantly, genes associated with lymphocyte activation and function demonstrated a significant increase in aged memory T cells, accompanied by upregulation of immunosuppressive markers and immune checkpoints, revealing an abnormal T cell function in aged cells. Furthermore, aging significantly affects T cell survival and death signaling. While aged CD4 memory T cells exhibited pro-apoptotic gene signatures, aged CD8 memory T cells expressed anti-apoptotic genes. Thus, the transcriptional analysis of gene expression and signaling pathways in aged T cell subsets shed light on our understanding of altered immune function with aging, which will have great potential for clinical interventions for older adults.
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http://dx.doi.org/10.3389/fcell.2020.624380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905051PMC
February 2021

TIGIT promotes CD8T cells exhaustion and predicts poor prognosis of colorectal cancer.

Cancer Immunol Immunother 2021 Feb 26. Epub 2021 Feb 26.

Department of Gastrointestinal Surgery, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510630, People's Republic of China.

TIGIT is a lymphocyte surface receptor, which is mainly expressed on the surface of CD8T cells. The role of TIGIT in colorectal cancer and its expression pattern in colorectal cancer infiltrating lymphocytes are still controversial. This study aimed at identifying the function of TIGIT in colorectal cancer. Patients with colorectal cancer showed significantly higher TIGITCD8T cell infiltration in tumor tissues, metastases compared with paired PBMC and normal tissues through flow cytometry. TIGITCD8T cells showed an exhausted phenotype and expressed low levels of killer cytokines IFN-γ, IL-2, TNF-α. In addition, more inhibitory receptors such as PD-1, LAG-3, and TIM-3 were expressed on the surface of TIGITCD8T cells. TGF-β1 could promote the expression of TIGIT and inhibit CD8T cell function in vitro. Moreover, the accumulation of TIGITT cells in tumors was associated with advanced disease, predicted early recurrence, and reduced survival rates in colorectal cancer patients. Our results indicate that TIGIT can be a biological marker for the prognosis of colorectal cancer, and TIGIT can be used as a potential target for treatment.
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http://dx.doi.org/10.1007/s00262-021-02886-8DOI Listing
February 2021

Discovery of TAK-981, a First-in-Class Inhibitor of SUMO-Activating Enzyme for the Treatment of Cancer.

J Med Chem 2021 Mar 25;64(5):2501-2520. Epub 2021 Feb 25.

Millennium Pharmaceuticals, a wholly owned subsidiary of Takeda Pharmaceuticals Company Ltd., Cambridge, Massachusetts 02139, United States.

SUMOylation is a reversible post-translational modification that regulates protein function through covalent attachment of small ubiquitin-like modifier (SUMO) proteins. The process of SUMOylating proteins involves an enzymatic cascade, the first step of which entails the activation of a SUMO protein through an ATP-dependent process catalyzed by SUMO-activating enzyme (SAE). Here, we describe the identification of TAK-981, a mechanism-based inhibitor of SAE which forms a SUMO-TAK-981 adduct as the inhibitory species within the enzyme catalytic site. Optimization of selectivity against related enzymes as well as enhancement of mean residence time of the adduct were critical to the identification of compounds with potent cellular pathway inhibition and ultimately a prolonged pharmacodynamic effect and efficacy in preclinical tumor models, culminating in the identification of the clinical molecule TAK-981.
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http://dx.doi.org/10.1021/acs.jmedchem.0c01491DOI Listing
March 2021

Ultrasound May Suppress Tumor Growth, Inhibit Inflammation, and Establish Tolerogenesis by Remodeling Innatome via Pathways of ROS, Immune Checkpoints, Cytokines, and Trained Immunity/Tolerance.

J Immunol Res 2021 9;2021:6664453. Epub 2021 Feb 9.

Centers for Cardiovascular Research and Inflammation, Translational, & Clinical Lung Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.

Background: The immune mechanisms underlying low-intensity ultrasound- (LIUS-) mediated suppression of inflammation and tumorigenesis remain poorly determined.

Methods: We used microarray datasets from the NCBI GEO DataSet repository and conducted comprehensive data-mining analyses, where we examined the gene expression of 1376 innate immune regulators (innatome genes (IGs) in cells treated with LIUS.

Results: We made the following findings: (1) LIUS upregulates proinflammatory IGs and downregulates metastasis genes in cancer cells, and LIUS upregulates adaptive immunity pathways but inhibits danger-sensing and inflammation pathways and promote tolerogenic differentiation in bone marrow (BM) cells. (2) LIUS upregulates IGs encoded for proteins localized in the cytoplasm, extracellular space, and others, but downregulates IG proteins localized in nuclear and plasma membranes, and LIUS downregulates phosphatases. (3) LIUS-modulated IGs act partially via several important pathways of reactive oxygen species (ROS), reverse signaling of immune checkpoint receptors B7-H4 and BTNL2, inflammatory cytokines, and static or oscillatory shear stress and heat generation, among which ROS is a dominant mechanism. (4) LIUS upregulates trained immunity enzymes in lymphoma cells and downregulates trained immunity enzymes and presumably establishes trained tolerance in BM cells. (5) LIUS modulates chromatin long-range interactions to differentially regulate IGs expression in cancer cells and noncancer cells.

Conclusions: Our analysis suggests novel molecular mechanisms that are utilized by LIUS to induce tumor suppression and inflammation inhibition. Our findings may lead to development of new treatment protocols for cancers and chronic inflammation.
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http://dx.doi.org/10.1155/2021/6664453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889351PMC
February 2021

Tissue Treg Secretomes and Transcription Factors Shared With Stem Cells Contribute to a Treg Niche to Maintain Treg-Ness With 80% Innate Immune Pathways, and Functions of Immunosuppression and Tissue Repair.

Front Immunol 2020 5;11:632239. Epub 2021 Feb 5.

Centers for Cardiovascular Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United States.

We used functional -omics angles and examined transcriptomic heterogeneity in CD4Foxp3 regulatory T cells (Treg) from spleen (s-Treg), lymph nodes (LN-Treg), intestine (int-Treg), and visceral adipose tissue (VAT-Treg), and made significant findings: Five new shared Treg genes including NIBAN, TNFRSF1b, DUSP4,VAV2, and KLRG1, and 68 new signatures are identified. Among 27 signaling pathways shared in four tissue Treg, 22 pathways are innate immune pathways (81.5%); s-Treg, LN-Treg, int-Treg, and VAT-Treg have zero, 49, 45, and 116 upregulated pathways, respectively; 12, 7, and 15 out of 373 CD markers are identified as specific for LN-Treg, int-Treg, and VAT-Treg, respectively, which may initiate innate immune signaling; 7, 49, 44, and 79 increased cytokines out of 1176 cytokines are identified for four Treg, respectively, suggesting that Treg have much more secretory proteins/cytokines than IL-10, TGF-β, and IL-35; LN-Treg, int-Treg, and VAT-Treg have 13 additional secretory functions more than s-Treg, found by analyzing 1,706 secretomic genes; 2, 20, 25, and 43 increased transcription factors (TFs) out of 1,496 TFs are identified four Treg, respectively; LN-Treg and int-Treg have increased pyroptosis regulators but VAT-Treg have increased apoptosis regulators; 1, 15, 19, and 31 increased kinases out of 661 kinome are identified for s-Treg, LN-Treg, int-Treg, and VAT-Treg, respectively; comparing with that of s-Treg, LN-Treg, int-Treg, and VAT-Treg increase activated cluster (clusters 1-3) markers; and decrease resting cluster (clusters 4-6) markers; and Treg promote tissue repair by sharing secretomes and TFs AHR, ETV5, EGR1, and KLF4 with stem cells, which partially promote upregulation of all the groups of Treg genes. These results suggest that stem cell-shared master genes make tissue Treg as the first T cell type using a Treg niche to maintain their Treg-ness with 80% innate immune pathways, and triple functions of immunosuppression, tissue repair, and homeostasis maintenance. Our results have provided novel insights on the roles of innate immune pathways on Treg heterogeneity and new therapeutic targets for immunosuppression, tissue repair, cardiovascular diseases, chronic kidney disease, autoimmune diseases, transplantation, and cancers.
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http://dx.doi.org/10.3389/fimmu.2020.632239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892453PMC
February 2021

Learning-Based Stopping Power Mapping on Dual-Energy CT for Proton Radiation Therapy.

Int J Part Ther 2021 12;7(3):46-60. Epub 2021 Feb 12.

Department of Radiation Oncology and Winship Cancer Institute, Emory University, Atlanta, GA, USA.

Purpose: Dual-energy computed tomography (DECT) has been used to derive relative stopping power (RSP) maps by obtaining the energy dependence of photon interactions. The DECT-derived RSP maps could potentially be compromised by image noise levels and the severity of artifacts when using physics-based mapping techniques. This work presents a noise-robust learning-based method to predict RSP maps from DECT for proton radiation therapy.

Materials And Methods: The proposed method uses a residual attention cycle-consistent generative adversarial network to bring DECT-to-RSP mapping close to a 1-to-1 mapping by introducing an inverse RSP-to-DECT mapping. To evaluate the proposed method, we retrospectively investigated 20 head-and-neck cancer patients with DECT scans in proton radiation therapy simulation. Ground truth RSP values were assigned by calculation based on chemical compositions and acted as learning targets in the training process for DECT datasets; they were evaluated against results from the proposed method using a leave-one-out cross-validation strategy.

Results: The predicted RSP maps showed an average normalized mean square error of 2.83% across the whole body volume and an average mean error less than 3% in all volumes of interest. With additional simulated noise added in DECT datasets, the proposed method still maintained a comparable performance, while the physics-based stoichiometric method suffered degraded inaccuracy from increased noise level. The average differences from ground truth in dose volume histogram metrics for clinical target volumes were less than 0.2 Gy for D and D with no statistical significance. Maximum difference in dose volume histogram metrics of organs at risk was around 1 Gy on average.

Conclusion: These results strongly indicate the high accuracy of RSP maps predicted by our machine-learning-based method and show its potential feasibility for proton treatment planning and dose calculation.
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http://dx.doi.org/10.14338/IJPT-D-20-00020.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886267PMC
February 2021

Synthetic dual-energy CT for MRI-only based proton therapy treatment planning using label-GAN.

Phys Med Biol 2021 Mar 9;66(6):065014. Epub 2021 Mar 9.

Department of Radiation Oncology and Winship Cancer Institute, Emory University, Atlanta, GA 30322, United States of America.

MRI-only treatment planning is highly desirable in the current proton radiation therapy workflow due to its appealing advantages such as bypassing MR-CT co-registration, avoiding x-ray CT exposure dose and reduced medical cost. However, MRI alone cannot provide stopping power ratio (SPR) information for dose calculations. Given that dual energy CT (DECT) can estimate SPR with higher accuracy than conventional single energy CT, we propose a deep learning-based method in this study to generate synthetic DECT (sDECT) from MRI to calculate SPR. Since the contrast difference between high-energy and low-energy CT (LECT) is important, and in order to accurately model this difference, we propose a novel label generative adversarial network-based model which can not only discriminate the realism of sDECT but also differentiate high-energy CT (HECT) and LECT from DECT. A cohort of 57 head-and-neck cancer patients with DECT and MRI pairs were used to validate the performance of the proposed framework. The results of sDECT and its derived SPR maps were compared with clinical DECT and the corresponding SPR, respectively. The mean absolute error for synthetic LECT and HECT were 79.98 ± 18.11 HU and 80.15 ± 16.27 HU, respectively. The corresponding SPR maps generated from sDECT showed a normalized mean absolute error as 5.22% ± 1.23%. By comparing with the traditional Cycle GANs, our proposed method significantly improves the accuracy of sDECT. The results indicate that on our dataset, the sDECT image form MRI is close to planning DECT, and thus shows promising potential for generating SPR maps for proton therapy.
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http://dx.doi.org/10.1088/1361-6560/abe736DOI Listing
March 2021

Thyroid gland delineation in noncontrast-enhanced CTs using deep convolutional neural networks.

Phys Med Biol 2021 Feb 16;66(5):055007. Epub 2021 Feb 16.

Department of Radiation Oncology and Winship Cancer Institute, Emory University, Atlanta, GA 30322, United States of America.

The purpose of this study is to develop a deep learning method for thyroid delineation with high accuracy, efficiency, and robustness in noncontrast-enhanced head and neck CTs. The cross-sectional analysis consisted of six tests, including randomized cross-validation and hold-out experiments, tests of prediction accuracy between cancer and benign and cross-gender analysis were performed to evaluate the proposed deep-learning-based performance method. CT images of 1977 patients with suspected thyroid carcinoma were retrospectively investigated. The automatically segmented thyroid gland volume was compared against physician-approved clinical contours using metrics, the Pearson correlation and Bland-Altman analysis. Quantitative metrics included: the Dice similarity coefficient (DSC), sensitivity, specificity, Jaccard index (JAC), Hausdorff distance (HD), mean surface distance (MSD), residual mean square distance (RMSD) and the center of mass distance (CMD). The robustness of the proposed method was further tested using the nonparametric Kruskal-Wallis test to assess the equality of distribution of DSC values. The proposed method's accuracy remained high through all the tests, with the median DSC, JAC, sensitivity and specificity higher than 0.913, 0.839, 0.856 and 0.979, respectively. The proposed method also resulted in median MSD, RMSD, HD and CMD, of less than 0.31 mm, 0.48 mm, 2.06 mm and 0.50 mm, respectively. The MSD and RMSD were 0.40 ± 0.29 mm and 0.70 ± 0.46 mm, respectively. Concurrent testing of the proposed method with 3D U-Net and V-Net showed that the proposed method had significantly improved performance. The proposed deep-learning method achieved accurate and robust performance through six cross-sectional analysis tests.
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http://dx.doi.org/10.1088/1361-6560/abc5a6DOI Listing
February 2021

A Color Restoration Algorithm for Diffractive Optical Images of Membrane Camera.

Sensors (Basel) 2021 Feb 4;21(4). Epub 2021 Feb 4.

College of Earth, Ocean, and Atmospheric Sciences, Oregon State University, Corvallis, OR 97331, USA.

In order to verify the technology of the membrane diffractive imaging system for Chinese next generation geo-stationary earth orbit (GEO) satellite, a series of ground experiments have been carried out using a membrane optical camera with 80 mm aperture (Φ80) lens. The inherent chromatic aberration due to diffractive imaging appears in the obtained data. To address the issue, an effective color restoration algorithm framework by matching, tailoring, and non-linearly stretching the image histograms is proposed in this letter. Experimental results show the proposed approach has good performances in color restoration of the diffractive optical images than previous methods. The effectiveness and robustness of the algorithm are also quantitatively assessed using various color deviation indexes. The results indicate that the chromatic aberration of diffractive images can be effectively removed by about 85%. Also, the proposed method presents reasonable computational efficiency.
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http://dx.doi.org/10.3390/s21041053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913842PMC
February 2021

Letrozole Versus Clomiphene Citrate and Natural Cycle: Endometrial Receptivity During Implantation Window in Women With Polycystic Ovary Syndrome.

Front Endocrinol (Lausanne) 2020 18;11:532692. Epub 2021 Jan 18.

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Objective: Numerous studies have reported on ovulation and pregnancy rates in patients with polycystic ovary syndrome (PCOS). However, relevant data on endometrial receptivity are limited. This study was conducted to compare endometrial receptivity during implantation windows among letrozole (LE), clomiphene citrate (CC), and natural cycle, and to assess the predictive value for pregnancy of observed indicators.

Methods: This randomized controlled trial study enrolled 270 patients with PCOS. Patients were given LE (n=90) at a dose of 2.5mg/day or CC (n=90) at a dose of 50 mg/day on cycle days 5-9 for ovulation induction. Patients in the natural cycle group (n=90) did not receive any drug for ovulation induction. Endometrial ultrasonic parameters, integrin αvβ3, and vascular endothelial growth factor (VEGF) concentrations in uterine secretion were detected during the implantation window. The endometrial receptivity, ovulation rate, pregnancy rates, and predictive value of observed indicators for pregnancy were analyzed.

Results: The successful ovulation rate did not differ between the LE group and CC group (>0.05). Endometrial ultrasonic parameters [endometrial thickness (ET), endometrial volume (EV), vascularization index (VI), flow index (FI), vascularization flow index (VFI)], integrin αvβ3, and VEGF concentrations in uterine fluid were significantly higher in the LE group compared with the CC group and natural cycle group (<0.05). The clinical pregnancy and ongoing pregnancy rates of the LE group were significantly higher than in the CC group (<0.05). Endometrial ultrasonic parameters (VI, FI, and VFI), integrin αvβ3, and VEGF concentrations in uterine fluid of all pregnancy groups were significantly higher compared with the no pregnancy group (<0.05), and the above parameters in ongoing pregnancy were significantly higher than in biochemical pregnancy (<0.05). The endometrial FI during the implantation window had the highest predictive value for pregnancy (AUC=0.889). The integrin αvβ3 in uterine fluid had better predictive value (AUC=0.876) than VEGF.

Conclusions: Endometrial receptivity during the implantation window of LE is superior to CC in PCOS women, which may be related to higher clinical pregnancy and ongoing pregnancy rates. Endometrial FI examined by 3-D power Doppler, and integrin αvβ3 in uterine secretion during the implantation window, could be preferable non-invasive predictor markers for pregnancy.

Clinical Trial Registration: www.chictr.org.cn, ChiCTR1900023423.
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http://dx.doi.org/10.3389/fendo.2020.532692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848032PMC
January 2021

A Novel Subset of CD95 Pro-Inflammatory Macrophages Overcome miR155 Deficiency and May Serve as a Switch From Metabolically Healthy Obesity to Metabolically Unhealthy Obesity.

Front Immunol 2020 7;11:619951. Epub 2021 Jan 7.

Cardiovascular Research Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United States.

Metabolically healthy obesity (MHO) accounts for roughly 35% of all obese patients. There is no clear consensus that has been reached on whether MHO is a stable condition or merely a transitory period between metabolically healthy lean and metabolically unhealthy obesity (MUO). Additionally, the mechanisms underlying MHO and any transition to MUO are not clear. Macrophages are the most common immune cells in adipose tissues and have a significant presence in atherosclerosis. Fas (or CD95), which is highly expressed on macrophages, is classically recognized as a pro-apoptotic cell surface receptor. However, Fas also plays a significant role as a pro-inflammatory molecule. Previously, we established a mouse model (ApoE/miR155; DKO mouse) of MHO, based on the criteria of not having metabolic syndrome (MetS) and insulin resistance (IR). In our current study, we hypothesized that MHO is a transition phase toward MUO, and that inflammation driven by our newly classified CD95CD86 macrophages is a novel mechanism for this transition. We found that, with extended (24 weeks) high-fat diet feeding (HFD), MHO mice became MUO, shown by increased atherosclerosis. Mechanistically, we found the following: at the MHO stage, DKO mice exhibited increased pro-inflammatory markers in adipose tissue, including CD95, and serum; total adipose tissue macrophages (ATMs) increased; CD95CD86 subset of ATMs also increased; and human aortic endothelial cells (HAECs) were activated (as determined by upregulated ICAM1 expression) when incubated with conditioned media from CD95-containing DKO ATMs and human peripheral blood mononuclear cells-derived macrophages in comparison to respective controls. These results suggest that extended HFD in MHO mice promotes vascular inflammation and atherosclerosis increasing CD95 pro-inflammatory ATMs. In conclusion, we have identified a novel molecular mechanism underlying MHO transition to MUO with HFD. We have also found a previously unappreciated role of CD95 macrophages as a potentially novel subset that may be utilized to assess pro-inflammatory characteristics of macrophages, specifically in adipose tissue in the absence of pro-inflammatory miR-155. These findings have provided novel insights on MHO transition to MUO and new therapeutic targets for the future treatment of MUO, MetS, other obese diseases, and type II diabetes.
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http://dx.doi.org/10.3389/fimmu.2020.619951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817616PMC
January 2021

High quality proton portal imaging using deep learning for proton radiation therapy: a phantom study.

Biomed Phys Eng Express 2020 04 27;6(3):035029. Epub 2020 Apr 27.

Department of Radiation Oncology and Winship Cancer Institute, Emory University, Atlanta, GA, United States of America.

Purpose; For shoot-through proton treatments, like FLASH radiotherapy, there will be protons exiting the patient which can be used for proton portal imaging (PPI), revealing valuable information for the validation of tumor location in the beam's-eye-view at native gantry angles. However, PPI has poor inherent contrast and spatial resolution. To deal with this issue, we propose a deep-learning-based method to use kV digitally reconstructed radiographs (DRR) to improve PPI image quality. Method; We used a residual generative adversarial network (GAN) framework to learn the nonlinear mapping between PPIs and DRRs. Residual blocks were used to force the model to focus on the structural differences between DRR and PPI. To assess the accuracy of our method, we used 149 images for training and 30 images for testing. PPIs were acquired using a double-scattered proton beam. The DRRs acquired from CT acted as learning targets in the training process and were used to evaluate results from the proposed method using a six-fold cross-validation scheme. Results; Qualitatively, the corrected PPIs showed enhanced spatial resolution and captured fine details present in the DRRs that are missed in the PPIs. The quantitative results for corrected PPIs show average normalized mean error (NME), normalized mean absolute error (NMAE), peak signal-to-noise ratio (PSNR) and structural similarity (SSIM) index of -0.1%, 0.3%, 39.14 dB, and 0.987, respectively. Conclusion; The results indicate the proposed method can generate high quality corrected PPIs and this work shows the potential to use a deep-learning model to make PPI available in proton radiotherapy. This will allow for beam's-eye-view (BEV) imaging with the particle used for treatment, leading to a valuable alternative to orthogonal x-rays or cone-beam CT for patient position verification.
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http://dx.doi.org/10.1088/2057-1976/ab8a74DOI Listing
April 2020

Head-and-neck organs-at-risk auto-delineation using dual pyramid networks for CBCT-guided adaptive radiotherapy.

Phys Med Biol 2021 Feb 11;66(4):045021. Epub 2021 Feb 11.

Department of Radiation Oncology, Emory University, Atlanta, GA, United States of America.

Organ-at-risk (OAR) delineation is a key step for cone-beam CT (CBCT) based adaptive radiotherapy planning that can be a time-consuming, labor-intensive, and subject-to-variability process. We aim to develop a fully automated approach aided by synthetic MRI for rapid and accurate CBCT multi-organ contouring in head-and-neck (HN) cancer patients. MRI has superb soft-tissue contrasts, while CBCT offers bony-structure contrasts. Using the complementary information provided by MRI and CBCT is expected to enable accurate multi-organ segmentation in HN cancer patients. In our proposed method, MR images are firstly synthesized using a pre-trained cycle-consistent generative adversarial network given CBCT. The features of CBCT and synthetic MRI (sMRI) are then extracted using dual pyramid networks for final delineation of organs. CBCT images and their corresponding manual contours were used as pairs to train and test the proposed model. Quantitative metrics including Dice similarity coefficient (DSC), Hausdorff distance 95% (HD95), mean surface distance, and residual mean square distance (RMS) were used to evaluate the proposed method. The proposed method was evaluated on a cohort of 65 HN cancer patients. CBCT images were collected from those patients who received proton therapy. Overall, DSC values of 0.87 ± 0.03, 0.79 ± 0.10/0.79 ± 0.11, 0.89 ± 0.08/0.89 ± 0.07, 0.90 ± 0.08, 0.75 ± 0.06/0.77 ± 0.06, 0.86 ± 0.13, 0.66 ± 0.14, 0.78 ± 0.05/0.77 ± 0.04, 0.96 ± 0.04, 0.89 ± 0.04/0.89 ± 0.04, 0.83 ± 0.02, and 0.84 ± 0.07 for commonly used OARs for treatment planning including brain stem, left/right cochlea, left/right eye, larynx, left/right lens, mandible, optic chiasm, left/right optic nerve, oral cavity, left/right parotid, pharynx, and spinal cord, respectively, were achieved. This study provides a rapid and accurate OAR auto-delineation approach, which can be used for adaptive radiation therapy.
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http://dx.doi.org/10.1088/1361-6560/abd953DOI Listing
February 2021

Facile synthesis of CeO/carbonate doped BiOCO Z-scheme heterojunction for improved visible-light photocatalytic performance: Photodegradation of tetracycline and photocatalytic mechanism.

J Colloid Interface Sci 2021 Apr 3;588:283-294. Epub 2021 Jan 3.

College of Environmental Science and Engineering, Hunan University, Changsha 410082, Hunan, PR China; Key Laboratory of Environmental Biology and Pollution Control (Hunan University), Ministry of Education, Changsha 410082, Hunan, PR China.

CeO nanoparticles are successfully loaded on carbonate doped BiOCO (CBOC) nanosheets by a facile hydrothermal and low-temperature calcination method. CeO/CBOC heterojunction shows significantly enhanced photocatalytic activity, when 35 mg of CeO/CBOC photocatalyst is added to tetracycline (TC) solution (20 mg/L, 100 mL), about 79.5% TC is degraded within 90 min under visible light irradiation, which is much higher than that of original CeO and CBOC. According to photoelectrochemical characterization and active radical capture experiments, the Z-scheme electron transfer mechanism is the reason for the significant enhancement of photocatalytic activity. Besides, the XPS results indicate that Ce/Ce redox pairs are formed at the contact interface between CeO and CBOC, which is conducive to the transfer of photoexcited electrons and production of superoxide radicals. Additionally, the photocatalytic mechanism and possible degradation pathway of TC is proposed through free radical trapping experiments and liquid chromatography-mass (LC-MS) analysis. This study will accumulate experience for the combination of CeO and bismuth-based nanomaterials, and provide a feasible way to design wide band-gap bismuth-based photocatalysts, thereby achieving efficient visible light degradation of environmental pollutants.
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http://dx.doi.org/10.1016/j.jcis.2020.12.073DOI Listing
April 2021