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  • Frontiers Media SA  (255)
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  • Frontiers Media SA  (255)
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  • 1
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Oncology Vol. 12 ( 2022-9-16)
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2022-9-16)
    Abstract: To compare and evaluate radiomics models to preoperatively predict β-catenin mutation in patients with hepatocellular carcinoma (HCC). Methods Ninety-eight patients who underwent preoperative gadobenate dimeglumine (Gd-BOPTA)-enhanced MRI were retrospectively included. Volumes of interest were manually delineated on arterial phase, portal venous phase, delay phase, and hepatobiliary phase (HBP) images. Radiomics features extracted from different combinations of imaging phases were analyzed and validated. A linear support vector classifier was applied to develop different models. Results Among all 15 types of radiomics models, the model with the best performance was seen in the R HBP radiomics model. The area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity of the R HBP radiomics model in the training and validation cohorts were 0.86 (95% confidence interval [CI], 0.75–0.93), 0.75, 1.0, and 0.65 and 0.82 (95% CI, 0.63–0.93), 0.73, 0.67, and 0.76, respectively. The combined model integrated radiomics features in the R HBP radiomics model, and signatures in the clinical model did not improve further compared to the single HBP radiomics model with AUCs of 0.86 and 0.76. Good calibration for the best R HBP radiomics model was displayed in both cohorts; the decision curve showed that the net benefit could achieve 0.15. The most important radiomics features were low and high gray-level zone emphases based on gray-level size zone matrix with the same Shapley additive explanation values of 0.424. Conclusion The R HBP radiomics model may be used as an effective model indicative of HCCs with β-catenin mutation preoperatively and thus could guide personalized medicine.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2649216-7
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  • 2
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Immunology Vol. 12 ( 2021-2-2)
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 12 ( 2021-2-2)
    Abstract: The high infection rate and rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) make it a world-wide pandemic. Individuals infected by the virus exhibited different degrees of symptoms, and most convalescent individuals have been shown to develop both cellular and humoral immune responses. However, virus-specific adaptive immune responses in severe patients during acute phase have not been thoroughly studied. Here, we found that in a group of COVID-19 patients with acute respiratory distress syndrome (ARDS) during hospitalization, most of them mounted SARS-CoV-2-specific antibody responses, including neutralizing antibodies. However, compared to healthy controls, the percentages and absolute numbers of both NK cells and CD8 + T cells were significantly reduced, with decreased IFNγ expression in CD4 + T cells in peripheral blood from severe patients. Most notably, their peripheral blood lymphocytes failed in producing IFNγ against viral proteins. Thus, severe COVID-19 patients at acute infection stage developed SARS-CoV-2-specific antibody responses but were impaired in cellular immunity, which emphasizes on the role of cellular immunity in COVID-19.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2606827-8
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  • 3
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 13 ( 2022-9-9)
    Abstract: Renal fibrosis is a common pathway for the progression of various chronic kidney diseases (CKD), and the formation and deterioration will eventually lead to end-stage renal failure, which brings a heavy medical burden to the world. HeidihuangWan (HDHW) is a herbal formulation with stable and reliable clinical efficacy in the treatment of renal fibrosis. However, the mechanism of HDHW in treating renal fibrosis is not clear. In this study, we aimed to investigate the mechanism of HDHW to improve renal fibrosis. Wistar rats were randomly divided into the normal control group, 5/6 Nephrectomy group, astragaloside IV (AS-IV) group, HDHW group, and HDHW + IGF-1R inhibitor (JB1) group. Except for the normal control group, the rat renal fibrosis model was established by 5/6 nephrectomy and intervened with drugs for 8 weeks. Blood samples were collected to evaluate renal function. Hematoxylin-Eosin (HE), Periodic Acid-Schiff (PAS), Modified Masson’s Trichrome (Masson) staining were used to evaluate the pathological renal injury, and immunohistochemistry and Western blotting were used to detect the protein expression of renal tissue. The results showed that HDHW was effective in improving renal function and reducing renal pathological damage. HDHW down-regulated the levels of fibrosis marker proteins, including α-smooth muscle actin (α-SMA), vimentin, and transforming growth factors–β(TGF-β), which in turn reduced renal fibrosis. Further studies showed that HDHW down-regulated the expression of autophagy-related proteins Beclin1 and LC3II, indicating that HDHW inhibited autophagy. In addition, we examined the activity of the class I phosphatidylinositol-3 kinase (PI3K)/serine-threonine kinase (Akt)/mTOR pathway, an important signaling pathway regulating autophagy, and the level of insulin-like growth factor 1 (IGF-1), an upstream activator of PI3K/Akt/mTOR. HDHW upregulated the expression of IGF-1 and activated the PI3K/Akt/mTOR pathway, which may be a vital pathway for its inhibition of autophagy. Application of insulin-like growth factor 1 receptor (IGF-1R) inhibitor further confirmed that the regulation of autophagy and renal fibrosis by HDHW was associated with IGF-1-mediated activation of the PI3K/Akt/mTOR pathway. In conclusion, our study showed that HDHW inhibited autophagy by upregulating IGF-1 expression, promoting the binding of IGF-1 to IGF-1R, and activating the PI3K/Akt/mTOR signaling pathway, thereby reducing renal fibrosis and protecting renal function. This study provides support for the application and further study of HDHW.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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  • 4
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Oncology Vol. 11 ( 2021-12-17)
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 11 ( 2021-12-17)
    Abstract: Radiologists’ diagnostic capabilities for breast mass lesions depend on their experience. Junior radiologists may underestimate or overestimate Breast Imaging Reporting and Data System (BI-RADS) categories of mass lesions owing to a lack of diagnostic experience. The computer-aided diagnosis (CAD) method assists in improving diagnostic performance by providing a breast mass classification reference to radiologists. This study aims to evaluate the impact of a CAD method based on perceptive features learned from quantitative BI-RADS descriptions on breast mass diagnosis performance. We conducted a retrospective multi-reader multi-case (MRMC) study to assess the perceptive feature-based CAD method. A total of 416 digital mammograms of patients with breast masses were obtained from 2014 through 2017, including 231 benign and 185 malignant masses, from which we randomly selected 214 cases (109 benign, 105 malignant) to train the CAD model for perceptive feature extraction and classification. The remaining 202 cases were enrolled as the test set for evaluation, of which 51 patients (29 benign and 22 malignant) participated in the MRMC study. In the MRMC study, we categorized six radiologists into three groups: junior, middle-senior, and senior. They diagnosed 51 patients with and without support from the CAD model. The BI-RADS category, benign or malignant diagnosis, malignancy probability, and diagnosis time during the two evaluation sessions were recorded. In the MRMC evaluation, the average area under the curve (AUC) of the six radiologists with CAD support was slightly higher than that without support (0.896 vs. 0.850, p = 0.0209). Both average sensitivity and specificity increased (p = 0.0253). Under CAD assistance, junior and middle-senior radiologists adjusted the assessment categories of more BI-RADS 4 cases. The diagnosis time with and without CAD support was comparable for five radiologists. The CAD model improved the radiologists’ diagnostic performance for breast masses without prolonging the diagnosis time and assisted in a better BI-RADS assessment, especially for junior radiologists.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2649216-7
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  • 5
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Ecology and Evolution Vol. 10 ( 2022-10-3)
    In: Frontiers in Ecology and Evolution, Frontiers Media SA, Vol. 10 ( 2022-10-3)
    Abstract: Clarifying the soil microbial metabolism and resource limitations could help to understand the functions and processes of aboveground ecosystems, as well as to predict ecosystem stability under global climate change. Karst tiankeng is a kind of large-scale negative surface terrain on the surface which is similar to an oasis in degraded karst landscapes, but their soil microbial resource limitations still unclear. In this study, we evaluated and compared the soil microbial resource limitation in non-degraded tiankeng (NDT), moderately degraded tiankeng (MDT), heavily degraded tiankeng (HDT), and outside tiankeng (OT) by calculating soil ecoenzymatic stoichiometry. Overall, soil microbial communities were more limited by C and P in karst tiankeng ecosystem. The soil microbial C and P limitations significantly differed with the karst tiankeng degradation increased, and the lowest C and P limitations were observed in NDT. The higher microbial C and P limitations were observed in OT. Linear regression and redundancy analysis indicated that soil microbial C and P limitations were significantly influenced by soil nutrients. Karst tiankeng degradation influence the biogeochemical cycle and function of karst tiankeng systems. Our results highlight that karst tiankeng (especially the NDT) can provide a stable habitat for the survival of microorganisms in karst areas. Karst tiankeng is essential for regional ecological restoration and biodiversity conservation.
    Type of Medium: Online Resource
    ISSN: 2296-701X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2745634-1
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  • 6
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Endocrinology Vol. 13 ( 2022-9-20)
    In: Frontiers in Endocrinology, Frontiers Media SA, Vol. 13 ( 2022-9-20)
    Abstract: In China, numerous human sperm banks only perform three-generation family history evaluation to exclude genetic diseases with clinical symptoms; therefore, many inherited risks cannot be detected before donor qualification even when a thorough genetic family history evaluation has been performed. Hence, the risk of recessive disease inheritance persists with the current eligibility guidelines in China regarding the donor selection process. Methods Retrospective study that reviewed the genetic test analyses and clinical outcomes of young adult men who were qualified sperm donors at the Hunan Province Human Sperm Bank of China from January 1, 2018, to May 1, 2021. We included a total of 3231 qualified sperm donors: all donors underwent primary screening for thalassemia and glucose-6-phosphate dehydrogenase (G6PD) deficiency. Whereafter, 278 of donors underwent genetic testing for specific genes, and 43 donors underwent whole exome sequencing. Results 2.4% of 3231 qualified sperm donors might have thalassemia and 1.4% might have G6PD deficiency. Sperm donors with thalassemia and G6PD deficiency would be eliminated. Specific gene testing identified 7 of the 278 donors (2.5%) as carriers of at least one pathogenic or likely pathogenic variant in a gene, including 1.9% of 154 donors (3/154) as carrier variants in α-Like or β-Like globin genes, 17.6% of 17 donors (3/17) as carrier variants in GJB2 , 12.5% of 8 donors (1/8) as carrier variants in SMN1 . In addition, among the 43 sperm donors carrying the 111 pathogenic/likely pathogenic variants, eight (18.6%) were carriers of pathogenic variants of the GJB2 gene. The frequency, therefore, was approximately 1 in 5. Conclusions The data suggest that used blood routine and RDT can make a preliminary screening of sperm donors, and special gene testing should be performed for sperm donors according to the regional incidence of specific genetic diseases. Meanwhile, whole exome sequencing can be used as a supplementary application in sperm donor genetic testing, and aid a successful and healthy pregnancy. However, industry guidelines must be modified to incorporate its use.
    Type of Medium: Online Resource
    ISSN: 1664-2392
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2592084-4
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  • 7
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2022-4-14)
    Abstract: Molecular subtypes of breast cancer are important references to personalized clinical treatment. For cost and labor savings, only one of the patient’s paraffin blocks is usually selected for subsequent immunohistochemistry (IHC) to obtain molecular subtypes. Inevitable block sampling error is risky due to the tumor heterogeneity and could result in a delay in treatment. Molecular subtype prediction from conventional H & amp;E pathological whole slide images (WSI) using the AI method is useful and critical to assist pathologists to pre-screen proper paraffin block for IHC. It is a challenging task since only WSI-level labels of molecular subtypes from IHC can be obtained without detailed local region information. Gigapixel WSIs are divided into a huge amount of patches to be computationally feasible for deep learning, while with coarse slide-level labels, patch-based methods may suffer from abundant noise patches, such as folds, overstained regions, or non-tumor tissues. A weakly supervised learning framework based on discriminative patch selection and multi-instance learning was proposed for breast cancer molecular subtype prediction from H & amp;E WSIs. Firstly, co-teaching strategy using two networks was adopted to learn molecular subtype representations and filter out some noise patches. Then, a balanced sampling strategy was used to handle the imbalance in subtypes in the dataset. In addition, a noise patch filtering algorithm that used local outlier factor based on cluster centers was proposed to further select discriminative patches. Finally, a loss function integrating local patch with global slide constraint information was used to fine-tune MIL framework on obtained discriminative patches and further improve the prediction performance of molecular subtyping. The experimental results confirmed the effectiveness of the proposed AI method and our models outperformed even senior pathologists, which has the potential to assist pathologists to pre-screen paraffin blocks for IHC in clinic.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2649216-7
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  • 8
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Veterinary Science Vol. 8 ( 2021-4-29)
    In: Frontiers in Veterinary Science, Frontiers Media SA, Vol. 8 ( 2021-4-29)
    Abstract: Swine hepatitis E (swine HE) is a new type of zoonotic infectious disease caused by the swine hepatitis E virus (swine HEV). Open reading frame 3 (ORF3) is an important virulent protein of swine HEV, but its function still is mainly unclear. In this study, we generated adenoviruses ADV4-ORF3 and ADV4 negative control (ADV4-NC), which successfully mediated overexpression of enhanced green fluorescent protein (EGFP)-ORF3 and EGFP, respectively, in HepG2 cells. High-throughput sequencing was used to screen for differentially expressed long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs). The cis -target genes of lncRNAs were predicted, functional enrichment (Gene Ontology [GO] and Kyoto Encyclopedia of Genes and Genomes [KEGG] ) was performed, and 12 lncRNAs with statistically significant different expressions ( p ≤ 0.05 and q ≤ 1) were selected for further quantitative real-time reverse transcription (qRT-PCR) validation. In HepG2 cells, we identified 62 significantly differentially expressed genes (DEGs) (6,564 transcripts) and 319 lncRNAs (124 known lncRNAs and 195 novel lncRNAs) that were affected by ORF3, which were involved in systemic lupus erythematosus, Staphylococcus aureus infection, signaling pathways pluripotency regulation of stem cells, the peroxisome proliferator-activated receptor (PPAR) signaling pathway, and platinum drug resistance pathways. Cis -target gene prediction identified 45 lncRNAs corresponding to candidate mRNAs, among which eight were validated by qRT-PCR: LINC02476 (two transcripts), RAP2C-AS1, AC016526, AL139099 , and ZNF337-AS1 (3 transcripts). Our results revealed that the lncRNA profile in host cells affected by ORF3, swine HEV ORF3, might affect the pentose and glucuronate interconversions and mediate the formation of obstructive jaundice by influencing bile secretion, which will help to determine the function of ORF3 and the infection mechanism and treatment of swine HE.
    Type of Medium: Online Resource
    ISSN: 2297-1769
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2834243-4
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  • 9
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 12 ( 2021-7-13)
    Abstract: T cell infiltration into tumors is essential for successful immunotherapy against solid tumors. Herein, we found that the expression of hyaluronic acid synthases (HAS) was negatively correlated with patient survival in multiple types of solid tumors including gastric cancer. HA impeded in vitro anti-tumor activities of anti-mesothelin (MSLN) chimeric antigen receptor T cells (CAR-T cells) against gastric cancer cells by restricting CAR-T cell mobility in vitro . We then constructed a secreted form of the human hyaluronidase PH20 (termed sPH20-IgG2) by replacing the PH20 signal peptide with a tPA signal peptide and attached with IgG2 Fc fragments. We found that overexpression of sPH20-IgG2 promoted CAR-T cell transmigration through an HA-containing matrix but did not affect the cytotoxicity or cytokine secretion of the CAR-T cells. In BGC823 and MKN28 gastric cancer cell xenografts, sPH20-IgG2 promoted anti-mesothelin CAR-T cell infiltration into tumors. Furthermore, mice infused with sPH20-IgG2 overexpressing anti-MSLN CAR-T cells had smaller tumors than mice injected with anti-MSLN CAR-T cells. Thus, we demonstrated that sPH20-IgG2 can enhance the antitumor activity of CAR-T cells against solid tumors by promoting CAR-T cell infiltration.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2606827-8
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  • 10
    In: Frontiers in Physics, Frontiers Media SA, Vol. 9 ( 2021-10-25)
    Abstract: A 1280 × 1,024 In 0.53 Ga 0.47 As short wave infrared (SWIR) focal plane array (FPA) detector with a planar-type back-illuminated process has been fabricated. With indium bump flip-chip bonding techniques, the InGaAs photodiode arrays were hybrid-integrated to the CMOS readout integrated circuit (ROIC) with correlated double sampling (CDS). The response spectrum is 0.9–1.7 μm. The test results show that the dark current density is 2.25 nA/cm 2 at 25 °C, the detectivity D * is up to 1.1 × 10 13  cm · Hz 1/2 /W, the noise electron is as low as 48 e − under correlated double sampling mode, the quantum efficiency is 88% at 1550 nm, and the operability is more than 99.9%. Moreover, the dark current and noise electron have been studied theoretically in depth. The results indicate that the diffusion current is the main contribution of the dark current, and the readout integrated circuit noise electron is the main source of FPA noise.
    Type of Medium: Online Resource
    ISSN: 2296-424X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2721033-9
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