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  • Frontiers Media SA  (344)
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  • 1
    Online Resource
    Online Resource
    Chimeric Antigens Receptor T Cell Therapy Improve the Prognosis of Pediatric Acute Lymphoblastic Leukemia With Persistent/Recurrent Minimal Residual Disease in First Complete Remission
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 12 ( 2022-1-7)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 12 ( 2022-1-7)
    Abstract: The presence of minimal residual disease (MRD) is an independent risk factor for poor prognosis in patients with acute lymphoblastic leukemia (ALL). Moreover, the role of chimeric antigen receptor T-cell (CAR-T) therapy in patients with MRD is currently unclear. Methods We conducted a prospective study to investigate the role of CAR-T therapy in patients with persistent/recurrent MRD-positive ALL in first remission. Results A total of 77 patients who had persistent/recurrent MRD were included. Of these patients, 43 were enrolled in the CAR-T group, 20 received chemotherapy as a bridge to allogeneic hematopoietic cell transplantation (allo-HSCT), and 14 patients received intensified chemotherapy. MRD negativity was achieved in 90.7% of the patients after CAR-T infusion. Patients who received CAR-T therapy had a higher 3-year leukemia-free survival (LFS) than patients who did not (77.8% vs. 51.1%, P = 0.033). Furthermore, patients in the CAR-T group had a higher 3-year LFS than those in the chemotherapy bridge-to-allo-HSCT group [77.8% (95% CI, 64.8–90.7%) vs. 68.7% (95% CI, 47.7–89.6%), P = 0.575] and had a significantly higher 3-year LFS than those in the intensified chemotherapy group [77.8% (95% CI, 64.8–90.7%) vs. 28.6% (95% CI, 4.9–52.3%), P = 0.001]. Among the patients who received CAR-T therapy, eight were not bridged to allo-HSCT, and six (75%) remained in remission with a median follow-up of 23.0 months after CAR-T infusion. Conclusions Our findings show that CAR-T therapy can effectively eliminate MRD and improve survival in patients with a suboptimal MRD response.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    DOI: 10.3389/fimmu.2021.731435
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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  • 2
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    Table_8.DOC
    Frontiers Media SA ; 2021
    In:  Frontiers in Medicine Vol. 8 ( 2021-6-2)
    Details
    In: Frontiers in Medicine, Frontiers Media SA, Vol. 8 ( 2021-6-2)
    Abstract: Background: Comprehensive rehabilitation programs are recommended for patients with prolonged mechanical ventilation (PMV) to facilitate functional recovery and ventilator weaning, but whether the functional status after rehabilitation influences outcome has not been clearly evaluated. This study aimed to investigate the association between post-rehabilitation functional status and weaning and survival outcome in PMV patients. Methods: We retrospectively enrolled PMV patients admitted to the respiratory care center (RCC), a post-ICU weaning facility with protocolized rehabilitation program, from January 2016 through December 2017. Functional status was measured by the de Morton Mobility Index (DEMMI), with a cut-off value set at 20 points. The primary outcomes were the weaning status at RCC discharge and hospital survival. The secondary outcomes were overall survival and survival at 3 months after RCC discharge. We followed patients until 3 months after RCC discharge or death. Logistic and Cox regressions were performed to identify significant parameters associated with weaning success and survival. Results: In total, 320 patients were enrolled. The weaning success rate was 71.6%. The survival rate at RCC discharge, hospital discharge, and 3 months after RCC discharge was 89.1, 77.5, and 66.6%, respectively. Post-rehabilitation DEMMI ≥ 20 (odds ratio [OR], 3.514; 95% confidence interval [CI] , 1.436–8.598; P = 0.006) was the most significantly associated with weaning success. The weaning success and higher post-rehabilitation DEMMI were the two most significant independent factors associated with both hospital survival (weaning success, OR, 12.272; 95% CI, 5.281–28.517; P & lt; 0.001; post-rehabilitation DEMMI ≥ 20, OR, 6.298; 95% CI, 1.302–30.477; P = 0.022) and survival at 3 months after RCC discharge (weaning success, OR, 38.788; 95% CI, 11.505–130.762; P & lt; 0.001; post-rehabilitation DEMMI ≥ 20, OR, 4.830; 95% CI, 1.072–21.756; P = 0.040). Post-rehabilitation DEMMI ≥ 20 remained significantly association with overall survival at 3 months after RCC discharge (hazard ratio, 0.237; 95% CI, 0.072–0.785; P = 0.018). Conclusions: Post-rehabilitation functional status of PMV patients was independently associated with weaning success, as well as hospital and 3-month overall survival after RCC discharge. Post-rehabilitation, but not pre-rehabilitation, functional status was a significant parameter associated with weaning success and survival in patients requiring PMV.
    Type of Medium: Online Resource
    ISSN: 2296-858X
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fmed.2021.675103
    DOI: 10.3389/fmed.2021.675103.s001
    DOI: 10.3389/fmed.2021.675103.s002
    DOI: 10.3389/fmed.2021.675103.s003
    DOI: 10.3389/fmed.2021.675103.s004
    DOI: 10.3389/fmed.2021.675103.s005
    DOI: 10.3389/fmed.2021.675103.s006
    DOI: 10.3389/fmed.2021.675103.s007
    DOI: 10.3389/fmed.2021.675103.s008
    DOI: 10.3389/fmed.2021.675103.s009
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2775999-4
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  • 3
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    DataSheet_4.pdf
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 13 ( 2022-12-21)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-12-21)
    Abstract: Drug repurposing is a fast and effective way to develop drugs for an emerging disease such as COVID-19. The main challenges of effective drug repurposing are the discoveries of the right therapeutic targets and the right drugs for combating the disease. Methods Here, we present a systematic repurposing approach, combining Homopharma and hierarchal systems biology networks (HiSBiN), to predict 327 therapeutic targets and 21,233 drug-target interactions of 1,592 FDA drugs for COVID-19. Among these multi-target drugs, eight candidates (along with pimozide and valsartan) were tested and methotrexate was identified to affect 14 therapeutic targets suppressing SARS-CoV-2 entry, viral replication, and COVID-19 pathologies. Through the use of in vitro (EC 50 = 0.4 μM) and in vivo models, we show that methotrexate is able to inhibit COVID-19 via multiple mechanisms. Results Our in vitro studies illustrate that methotrexate can suppress SARS-CoV-2 entry and replication by targeting furin and DHFR of the host, respectively. Additionally, methotrexate inhibits all four SARS-CoV-2 variants of concern. In a Syrian hamster model for COVID-19, methotrexate reduced virus replication, inflammation in the infected lungs. By analysis of transcriptomic analysis of collected samples from hamster lung, we uncovered that neutrophil infiltration and the pathways of innate immune response, adaptive immune response and thrombosis are modulated in the treated animals. Conclusions We demonstrate that this systematic repurposing approach is potentially useful to identify pharmaceutical targets, multi-target drugs and regulated pathways for a complex disease. Our findings indicate that methotrexate is established as a promising drug against SARS-CoV-2 variants and can be used to treat lung damage and inflammation in COVID-19, warranting future evaluation in clinical trials.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2022.1080897
    DOI: 10.3389/fimmu.2022.1080897.s001
    DOI: 10.3389/fimmu.2022.1080897.s002
    DOI: 10.3389/fimmu.2022.1080897.s003
    DOI: 10.3389/fimmu.2022.1080897.s004
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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  • 4
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    Table_5.doc
    Frontiers Media SA ; 2021
    In:  Frontiers in Immunology Vol. 12 ( 2021-10-4)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 12 ( 2021-10-4)
    Abstract: To avoid graft rejection, the hematopoietic stem cells with matched classical human leukocyte antigen (HLA) alleles are the primary choice for clinical allogeneic transplantation. However, even if the fully HLA-matched hematopoietic stem cells are used for transplantation, some patients still have poor prognosis after hematopoietic stem cell transplantation (HSCT), suggesting that the HLA system was not the only determinant of the outcomes of HSCT. In this study, we investigated whether the single-nucleotide polymorphisms (SNPs) of the co-stimulatory genes within non-HLA regions were related to the outcomes of HSCT. The genomic DNAs of 163 patients who had acute leukemia and received HSCT and their respective donors were collected for analysis. Thirty-four SNPs located in the four co-stimulatory genes including cytotoxic T-lymphocyte associated protein 4 (CTLA4), CD28, tumor necrosis factor ligand superfamily 4 (TNFSF4), and programmed cell death protein 1 (PDCD1) were selected to explore their relationship with the adverse outcomes after transplantation, including mortality, cytomegalovirus infection, graft-versus-host disease, and relapse. Our results revealed that nine SNPs in the CTLA4 gene, five SNPs in the PDCD1 gene, two SNPs in the TNFSF4 gene, and four SNPs in the CD28 gene were significantly associated with the occurrence of adverse outcomes post-HSCT. These SNPs may play important roles in immune response to allografts post-HSCT and can be the targets for developing strategy to identify appropriate donors.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2021.730507
    DOI: 10.3389/fimmu.2021.730507.s001
    DOI: 10.3389/fimmu.2021.730507.s002
    DOI: 10.3389/fimmu.2021.730507.s003
    DOI: 10.3389/fimmu.2021.730507.s004
    DOI: 10.3389/fimmu.2021.730507.s005
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
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  • 5
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    Data_Sheet_1.PDF
    Frontiers Media SA ; 2022
    In:  Frontiers in Microbiology Vol. 13 ( 2022-8-2)
    Details
    In: Frontiers in Microbiology, Frontiers Media SA, Vol. 13 ( 2022-8-2)
    Abstract: Cyanobacteriochromes (CBCRs) bind linear tetrapyrrole chromophores, mostly phycocyanobilin (PCB), and exhibit considerable spectral diversity with a high potential for biotechnological applications. Particular attention has been given to the conversion into intrinsic biliverdin (BV) incorporation due to the absence of PCB in mammalian cells. Our recent study discovered that a red/green CBCR of Spirulina subsalsa , SPI1085g3, was covalently attached to PCB and exhibited strong red fluorescence with a unique red/dark switch. In this study, we found that SPI1085g3 could be modestly chromophorylated with BV and absorb somewhat shifted (10 nm) red light, while the single C448S mutant could efficiently bind BV and exhibit unidirectional photoconversion and moderate dark reversion. The fluorescence in its dark-adapted state was switched off by red light, followed by a moderate recovery in the dark, and these were properties similar to those of PCB-binding SPI1085g3. Furthermore, by introducing the CY motif into the conserved CH motif for chromophore attachment, we developed another variant, C448S_CY, which showed increased BV-binding efficiency. As expected, C448S_CY had a significant enhancement in fluorescence quantum yield, reaching that of PCB-binding SPI1085g3 (0.14). These BV-binding CBCRs offer an improved platform for the development of unique photoswitchable fluorescent proteins compared with PCB-binding CBCRs.
    Type of Medium: Online Resource
    ISSN: 1664-302X
    URL: Article
    URL: Article
    DOI: 10.3389/fmicb.2022.952678
    DOI: 10.3389/fmicb.2022.952678.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587354-4
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  • 6
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    Data_Sheet_1.docx
    Frontiers Media SA ; 2020
    In:  Frontiers in Immunology Vol. 11 ( 2020-9-11)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 11 ( 2020-9-11)
    Abstract: Background: The eosinophilic inflammation plays a critical role in myocarditis (Mcd); its underlying mechanism remains to be further elucidated. This study aims to investigate the role of Bcl2-like protein 12 (Bcl2L12) in inducing the defects of apoptosis in eosinophils (Eos) of the heart tissues. Methods: Human explant heart samples were collected. Eosinophilia and myocarditis (Mcd)-like inflammation were induced in the mouse heart by immunizing with murine cardiac α-myosin heavy chain (MyHCα) peptides. Results: Markedly more Eos were observed in heart tissues from patients with Mcd than those from patients with dilated cardiomyopathy. Eos isolated from Mcd hearts showed the signs of apoptosis defects. The Eo counts in the Mcd heart tissues were positively correlated with the Bcl2L12 expression in Eos isolated from the heart tissues. Exposure to interleukin 5 in the culture induced the expression of Bcl2L12 in Eos. Bcl2L12 bound c-Myc, the transcription factor of Fas ligand (FasL), to prevent c-Myc from binding to the FasL promoter, to restrict the FasL gene transcription in Eos. Inhibition of Bcl2L12 prevented the induction of eosinophilia and Mcd-like inflammation in the mouse heart. Conclusions: The Bcl2L12 expression contributes to apoptosis defects in Eos of the Mcd heart. Blocking Bcl2L12 prevents the eosinophilia induction and alleviates Mcd-like inflammation in mice.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2020.01955
    DOI: 10.3389/fimmu.2020.01955.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2020
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  • 7
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    DataSheet_1.docx
    Frontiers Media SA ; 2021
    In:  Frontiers in Oncology Vol. 11 ( 2021-7-7)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 11 ( 2021-7-7)
    Abstract: Immune checkpoint inhibitors (ICIs) have been approved to treat patients with various cancer types, including lung cancer, in many countries. This study aims to investigate the effectiveness and safety of ICIs under different treatment conditions of non-small cell lung cancer patients. A population-based retrospective cohort study was conducted using the electronic health records of three medical centers in Taiwan. From January 01, 2016, to November 30, 2018, a total of 91 ICIs and 300 traditional chemotherapy users who had undergone stage III and IV lung cancer treatment were included in the study. We performed the randomized matched pair design by selecting a Chemotherapy subject for each ICI patient in the sample population. All subjects were monitored from the date of taking ICIs or chemotherapy drugs until the event of death, loss to follow-up, or were occurred with any defined adverse events. Kaplan-Meier estimators and cox proportional hazard regression models were used to compute the overall survival, efficacy, and safety of the ICIs group. The median overall survival (OS) in the ICI and Chemo groups after matching was 11.2 months and 10.5 months, respectively. However, the results showed no significant OS differences between ICIs and chemo groups for both before and after matching (HR,1.30; 95%CI, 0.68-2.46; p=0.428 before matching and HR,0.96; 95CI%, 0.64-1.44; p=0.838 after matching). We observed that with the higher amount of PD-L1, the length of the patients’ overall survival was (positive vs. negative PD-L1, HR,0.21; 95%CI, 0.05-0.80; p=0.022). The incidences of serious adverse drug events above grade 3 in the ICIs and traditional chemo groups were 12.7% and 21.5%, respectively. We also found that the number of AEs was less in ICIs than in the Chemo group, and the AEs that occurred after treatments were observed earlier in the ICIs compared to the Chemo group. ICIs drugs were observed to be safer than traditional chemotherapy as they had a lower risk of serious adverse drug events. It is necessary to pay attention to immune-related side effects and provide appropriate treatment. Furthermore, the patient’s physical status and PD-L1 test can be used to evaluate the clinical effectiveness of ICIs.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    URL: Article
    DOI: 10.3389/fonc.2021.671127
    DOI: 10.3389/fonc.2021.671127.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2649216-7
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  • 8
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    Table_3.DOCX
    Frontiers Media SA ; 2022
    In:  Frontiers in Medicine Vol. 9 ( 2022-4-25)
    Details
    In: Frontiers in Medicine, Frontiers Media SA, Vol. 9 ( 2022-4-25)
    Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is believed to have originated in Wuhan City, Hubei Province, China, in December 2019. Infection with this highly dangerous human-infecting coronavirus via inhalation of respiratory droplets from SARS-CoV-2 carriers results in coronavirus disease 2019 (COVID-19), which features clinical symptoms such as fever, dry cough, shortness of breath, and life-threatening pneumonia. Several COVID-19 waves arose in Taiwan from January 2020 to March 2021, with the largest outbreak ever having a high case fatality rate (CFR) (5.95%) between May and June 2021. In this study, we identified five 20I (alpha, V1)/B.1.1.7/GR SARS-CoV-2 (KMUH-3 to 7) lineage viruses from COVID-19 patients in this largest COVID-19 outbreak. Sequence placement analysis using the existing SARS-CoV-2 phylogenetic tree revealed that KMUH-3 originated from Japan and that KMUH-4 to KMUH-7 possibly originated via local transmission. Spike mutations M1237I and D614G were identified in KMUH-4 to KMUH-7 as well as in 43 other alpha/B.1.1.7 sequences of 48 alpha/B.1.1.7 sequences deposited in GISAID derived from clinical samples collected in Taiwan between 20 April and July. However, M1237I mutation was not observed in the other 12 alpha/B.1.1.7 sequences collected between 26 December 2020, and 12 April 2021. We conclude that the largest COVID-19 outbreak in Taiwan between May and June 2021 was initially caused by the alpha/B.1.1.7 variant harboring spike D614G + M1237I mutations, which was introduced to Taiwan by China Airlines cargo crew members. To our knowledge, this is the first documented COVID-19 outbreak caused by alpha/B.1.1.7 variant harboring spike M1237I mutation thus far. The largest COVID-19 outbreak in Taiwan resulted in 13,795 cases and 820 deaths, with a high CFR, at 5.95%, accounting for 80.90% of all cases and 96.47% of all deaths during the first 2 years. The high CFR caused by SARS-CoV-2 alpha variants in Taiwan can be attributable to comorbidities and low herd immunity. We also suggest that timely SARS-CoV-2 isolation and/or sequencing are of importance in real-time epidemiological investigations and in epidemic prevention. The impact of D614G + M1237I mutations in the spike gene on the SARS-CoV-2 virus spreading as well as on high CFR remains to be elucidated.
    Type of Medium: Online Resource
    ISSN: 2296-858X
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fmed.2022.869818
    DOI: 10.3389/fmed.2022.869818.s001
    DOI: 10.3389/fmed.2022.869818.s002
    DOI: 10.3389/fmed.2022.869818.s003
    DOI: 10.3389/fmed.2022.869818.s004
    DOI: 10.3389/fmed.2022.869818.s005
    DOI: 10.3389/fmed.2022.869818.s006
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2775999-4
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  • 9
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    Corrigendum: Identification and analysis of SARS-CoV-2 alpha variants in the largest Taiwan COVID-19 outbreak in 2021
    Frontiers Media SA ; 2023
    In:  Frontiers in Medicine Vol. 10 ( 2023-5-17)
    Details
    In: Frontiers in Medicine, Frontiers Media SA, Vol. 10 ( 2023-5-17)
    Type of Medium: Online Resource
    ISSN: 2296-858X
    URL: Article
    DOI: 10.3389/fmed.2023.1211944
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
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  • 10
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    Table3.XLS
    Frontiers Media SA ; 2023
    In:  Frontiers in Earth Science Vol. 11 ( 2023-8-10)
    Details
    In: Frontiers in Earth Science, Frontiers Media SA, Vol. 11 ( 2023-8-10)
    Abstract: The Jiaodong Peninsula is China’s largest gold province and the third largest in the world. Although gold mineralization is associated with Mesozoic granites temporally and spatially, the specific genetic association remains unclear, leading to ambiguity regarding the genetic type of gold deposits. To address this issue, we conducted whole-rock major and trace elements, LA–ICP–MS zircon U–Pb geochronology and trace elements geochemical analyses on the Linglong (Linglong suite), Yashan, and Nansu (Weideshan suite) plutons, and compiled contemporaneous magmatic rock data. Our results show that the granites were emplaced at 161 ± 2, 118 ± 1, and 121 ± 2 Ma, respectively. Geochemically, these rocks exhibit high Al 2 O 3 (12.73–14.10 wt%) content and Sr/Y (35.54–136.50) ratio, and low Y (3.26–11.20 ppm) and Yb (0.33–0.97 ppm) contents, indicating the adakitic rock properties. They were formed through partial melting of the thickened lower crust associated with subduction of the paleo-Pacific Plate. The Early Cretaceous granites contain a large amount of mafic microgranular enclaves, indicating the presence of mantle material mixing in the source area. Zircon trace elements show that the pre-mineralization magma (Linglong) had relatively low oxygen fugacity and temperature (ΔFMQ = −2.5 to +1.9, T-Ti in zircon (mean) = 740°C) compared to the mineralization magma (ΔFMQ = +0.5 to +3.9, T-Ti in zircon (mean) = 755°C). The physicochemical conditions in the pre-mineralization magma source area may be favorable for sulfide accumulation (may including gold). During the Early Cretaceous, North China Craton decratonization reached its climax, and a large number of adakitic crust-mantle mixed oxidized magma upwells, allowing for the migration and mineralization of a large amount of sulfides and gold. This model helps explain the transient, explosive, and genetic categories in Jiaodong gold deposits.
    Type of Medium: Online Resource
    ISSN: 2296-6463
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/feart.2023.1243844
    DOI: 10.3389/feart.2023.1243844.s001
    DOI: 10.3389/feart.2023.1243844.s002
    DOI: 10.3389/feart.2023.1243844.s003
    DOI: 10.3389/feart.2023.1243844.s004
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2741235-0
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