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  • 1
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-10-28)
    Abstract: Despite the initially reported high efficacy of vaccines directed against ancestral SARS-CoV-2, repeated infections in both unvaccinated and vaccinated populations remain a major global health challenge. Because of mutation-mediated immune escape by variants-of-concern (VOC), approved neutralizing antibodies (neutAbs) effective against the original strains have been rendered non-protective. Identification and characterization of mutation-independent pan-neutralizing antibody responses are therefore essential for controlling the pandemic. Here, we characterize and discuss the origins of SARS-CoV-2 neutAbs, arising from either natural infection or following vaccination. In our study, neutAbs in COVID-19 patients were detected using the combination of two lateral flow immunoassay (LFIA) tests, corroborated by plaque reduction neutralization testing (PRNT). A point-of-care neutAb LFIA, NeutraXpress™, was validated using serum samples from historical pre-COVID-19 negative controls, patients infected with other respiratory pathogens, and PCR-confirmed COVID-19 patients. Surprisingly, potent neutAb activity was mainly noted in patients generating both IgM and IgG against the Spike receptor-binding domain (RBD), in contrast to samples possessing anti-RBD IgG alone. We propose that low-affinity, high-avidity, germline-encoded natural IgM and subsequent generation of class-switched IgG may have an underappreciated role in cross-protection, potentially offsetting immune escape by SARS-CoV-2 variants. We suggest Reverse Vaccinology 3.0 to further exploit this innate-like defense mechanism. Our proposition has potential implications for immunogen design, and provides strategies to elicit pan-neutAbs from natural B1-like cells. Refinements in future immunization protocols might further boost long-term cross-protection, even at the mucosal level, against clinical manifestations of COVID-19.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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  • 2
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Public Health Vol. 10 ( 2022-9-8)
    In: Frontiers in Public Health, Frontiers Media SA, Vol. 10 ( 2022-9-8)
    Abstract: Understanding renal function state transition risk and associated factors in community residences is vital for appropriate preventive and care actions. We aim to investigate factors affecting renal function state transitions through 10-year longitudinal community screening surveys. Methods The prospective cohort study included participants who attended the screening program ≥2 times from 2001 to 2009 and were divided into two cohorts: those with baseline estimated glomerular filtration rate (eGFR) ≥60 ( n = 46,278) and those with eGFR 59–30 mL/min/1.73 m 2 ( n = 4,656). We applied the illness-death model to identify associated factors with eGFR & lt;60 and death for the cohort with baseline eGFR ≥60 and eGFR & lt;30 and death for that with baseline eGFR ≥59–30. Results Among the followed-up participants, 3,018 (6.5%) in the cohort of baseline eGFR ≥60 mL/min/1.73 m 2 and 322 (6.9%) in the cohort of eGFR 59–30 mL/min/1.73 m 2 experienced renal function state transition during a median over 7-year follow-up. Besides eGFR and grade of proteinuria, diabetes mellitus (adding nearly 50% hazard rate) is the main factor associated with both state transitions. Other early-phase eGFR state transition risk factors were metabolic syndrome score, triglyceride, uric acid, fasting blood sugar, and high-density lipoprotein cholesterol. Males, poor hemoglobin, high triglyceride, and high low-density lipoprotein cholesterol were all linked with the late-phase eGFR state transition hazard rate. Conclusion The study developed the state transition functions for community participants with varying renal function levels. Further actions to develop precision screening plans and services that incorporate personal risk factors and state transition risks are necessary.
    Type of Medium: Online Resource
    ISSN: 2296-2565
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2711781-9
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  • 3
    In: Frontiers in Public Health, Frontiers Media SA, Vol. 10 ( 2023-1-6)
    Abstract: Although early dementia detection is crucial to optimize the treatment outcomes and the management of associated symptoms, the published literature is scarce regarding the effectiveness of active screening protocols in enhancing dementia awareness and increasing the rate of early detection. The present study compared the detection ratio of an active community-based survey for dementia detection with the detection ratio of passive screening during routine clinical practice. Data for passive screening were obtained from the National Health Insurance (NHI) system, which was prospectively collected during the period from 2000 to 2003. Design A population-based cohort study with historical control. Setting Taiwan. Participants A total of 183 participants aged 65 years or older were involved in a community-based survey. Data from 1,921,308 subjects aged 65 years or older were retrieved from the NHI system. Measurements An adjusted detection ratio, defined as a ratio of dementia prevalence to incidence was used. Results The results showed that the dementia prevalence during the 2000–2003 period was 2.91% in the elderly population, compared with a prevalence of 6.59% when the active survey was conducted. The incidence of dementia in the active survey cohort was 1.83%. Overall, the dementia detection ratio was higher using active surveys [4.23, 95% confidence interval (CI): 2.68–6.69] than using passive detection (1.45, 95% CI: 1.43–1.47) for those aged 65–79 years. Similar findings were observed for those aged 80 years and older. Conclusion The implementation of an active community-based survey led to a 3-fold increase in the detection rate of early dementia detection compared to passive screening during routine practice.
    Type of Medium: Online Resource
    ISSN: 2296-2565
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2711781-9
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  • 4
    In: Frontiers in Chemistry, Frontiers Media SA, Vol. 10 ( 2022-10-19)
    Abstract: Current treatment of Helicobacter pylori involves a triple therapy comprising one proton pump inhibitor and two other antibiotics; however, the outcomes are limited due to the existence of antibiotic resistant strains. We previously reported that moenomycin A, a cell-wall transglycosylase inhibitor, is highly active against multidrug-resistant Helicobacter pylori . Herein we show that combination of moenomycin A with the protein synthesis inhibitor clarithromycin or metronidazole can synergistically achieve almost 95% eradication of multidrug-resistant Helicobacter pylori . We also found that the moenomycin A-non-susceptible strains of Helicobacter pylori with deletion of transglycosylase exhibit moenomycin A hyposensitivity, faster growth and impaired biofilm formation compared to the parental strain. Overall, the combination of moenomycin A and clarithromycin or metronidazole to achieve a synergistic effect on different targets is a promising treatment for multidrug-resistant Helicobacter pylori .
    Type of Medium: Online Resource
    ISSN: 2296-2646
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2711776-5
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  • 5
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Cardiovascular Medicine Vol. 9 ( 2022-3-2)
    In: Frontiers in Cardiovascular Medicine, Frontiers Media SA, Vol. 9 ( 2022-3-2)
    Abstract: Veno-arterial extracorporeal membrane oxygenation (ECMO) is increasingly used to treat high-risk pulmonary embolism (PE). However, its efficacy and safety remain uncertain. This retrospective cohort study aimed to determine whether ECMO could improve the clinical outcomes of patients with high-risk PE. Methods Forty patients with high-risk PE, who were admitted to Kaohsiung Chang Gung Memorial Hospital between January 2012 and December 2019, were included in this study. Demographic data and clinical outcomes were compared between patients treated without ECMO (non-ECMO group) and those treated with ECMO (ECMO group). Appropriate statistical tools were used to compare variables between groups and the survival was analyzed using the Kaplan–Meier method. Results The overall in-hospital mortality rate was 55%, in which 65% (26/40) of patients presented with cardiac arrest with a mortality rate of 77%, which was higher than that of patients without cardiac arrest (14%). There was no significant difference in major complications and in-hospital mortality between the non-ECMO and ECMO groups. However, in subgroup analysis, compared with patients treated without ECMO, earlier ECMO treatment was associated with a reduced risk of cardiac arrest ( P = 0.023) and lower in-hospital mortality ( P = 0.036). A log-rank test showed a significantly higher cumulative overall survival in the earlier ECMO treatment group ( P = 0.033). Conclusions In this retrospective cohort study, earlier ECMO treatment was associated with lower in-hospital mortality among unstable patients without cardiac arrest. Our findings suggest that ECMO can be considered as an initial treatment option for patients with high-risk PE in higher-volume hospitals.
    Type of Medium: Online Resource
    ISSN: 2297-055X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2781496-8
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  • 6
    Online Resource
    Online Resource
    Frontiers Media SA ; 2023
    In:  Frontiers in Cardiovascular Medicine Vol. 9 ( 2023-1-9)
    In: Frontiers in Cardiovascular Medicine, Frontiers Media SA, Vol. 9 ( 2023-1-9)
    Abstract: Computed tomography (CT) has been increasingly used in the diagnosis of acute aortic syndrome, and a number of high-risk CT imaging features have been reported. We aimed to identify CT imaging findings suggesting high-risk for acute aortic syndrome by examining clinical outcomes of patients with acute type A aortic intramural hematoma (TAIMH). Methods This retrospective study analyzed the relationship of clinical patient characteristics and imaging features with mortality and aortic events in 63 patients receiving initial medical treatment for TAIMH. Multivariate regression analysis was used to determine the predictors of aortic events, and the Kaplan–Meier method was used to analyze survival and aortic events. Results During a median follow-up of 4.2 years, 25 patients experienced aortic events and 40% of these occurred within 7 days of admission. In total, 12 patients experienced aortic death and 12 patients underwent open aortic surgery or endovascular stenting for aortic disease. In multivariate regression analysis, penetrating atherosclerotic ulcers (PAUs) or ulcer-like projections (ULPs) ( P = 0.04) and pericardial effusion ( P = 0.03) were independent predictors of aortic events. In the Cox regression model, PAUs/ULPs ( P = 0.04) and pericardial effusion ( P = 0.04) were independently associated with lower aortic event-free survival. Conclusion Identification of high-risk CT features is important for clinical decision-making during TAIMH treatment. Early and frequent CT imaging follow-up is required in patients receiving medical treatment. PAUs/ULP and pericardial effusion were the strongest predictors of adverse aortic events.
    Type of Medium: Online Resource
    ISSN: 2297-055X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2781496-8
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  • 7
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 13 ( 2023-8-15)
    Abstract: Breast cancer is the most common cancer type that affects women. In hormone receptor–positive (HR+), human epidermal growth factor receptor 2−negative (HER2–) advanced breast cancer (ABC), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha ( PIK3CA) is the most frequently mutated gene associated with poor prognosis. This study evaluated the frequency of PIK3CA mutations in the Taiwanese breast cancer population. Methodology This is a retrospective study; patient data were collected for 2 years from a next-generation sequencing database linked to electronic health records (EHRs). The primary endpoint was the regional prevalence of PIK3CA mutation. The secondary endpoints were to decipher the mutation types across breast cancer subtype, menopausal status, and time to treatment failure after everolimus (an mTOR inhibitor) or cyclin-dependent kinase 4/6 (CDK4/6) inhibitor treatment. Results PIK3CA mutations were identified in 278 of 728 patients (38%). PIK3CA mutations were reported in 43% of patients with HR−/HER2+ subtype and 42% of patients with HR+/HER2– postmenopausal status. A lower prevalence of PIK3CA mutations was observed in triple-negative (27%) and HR+/HER2– premenopausal patients (29%). The most common mutation was at exon 20 (H1047R mutation, 41.6%), followed by exon 9 (E545K mutation, 18.9% and E542K mutation, 10.3%). Among patients treated with CDK4/6 inhibitors, the median time to treatment failure was 12 months (95% CI: 7-21 months) in the PIK3CA mutation cohort and 16 months (95% CI: 11-23 months) in the PIK3CA wild-type cohort, whereas patients receiving an mTOR inhibitor reported a median time to treatment failure of 20.5 months (95% CI: 8-33 months) in the PIK3CA mutation cohort and 6 months (95% CI: 2-9 months) in the PIK3CA wild-type cohort. Conclusion A high frequency of PIK3CA mutations was detected in Taiwanese patients with breast cancer, which was consistent with previous studies. Early detection of PIK3CA mutations might influence therapeutic decisions, leading to better treatment outcomes.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2649216-7
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  • 8
    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
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2649216-7
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  • 9
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Oncology Vol. 12 ( 2022-6-29)
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2022-6-29)
    Abstract: B cells and B cell-related gene signatures in the tumor microenvironment (TME) are associated with the efficacy of anti-programmed cell death-1 (anti-PD-1) therapy in several cancer types, but not known for esophageal squamous cell carcinoma (ESCC). Patients and Methods Patients with advanced ESCC receiving anti-PD-1/PD-L1-based therapy were retrospectively included. A targeted RNA profiling of 770 immune-related genes from archival ESCC tissues was performed. Differential immune-related pathways and the levels of infiltrating immune cells were estimated through Gene Set Enrichment Analysis and CIBERSORT, respectively. CD19 and CD138 expression were evaluated through immunohistochemistry (IHC). The markers evaluated were correlated with clinical benefit (CB; defined as either objective response or stable disease for ≥6 months) and survival. Results A total of 64 patients were enrolled. The transcriptome analysis based on 25 patients revealed that B cell signature was significantly increased in patients with CB ( P & lt;.05) and correlated with a longer PFS ( P = .032) and OS ( P = .013). Multiple genes representative of B cells, B cell functions, and plasma cells were upregulated in patients with CB. On further analysis of B cell subtypes in patients with CB, increase of naïve B cells ( P = .057) and plasma cells ( P & lt;.01) was found but not memory B cells ( P = .27). The CD19 expression in tumor stroma, detected by IHC, was higher in patients with CB ( P = .033). Conclusion B cells in the TME were associated with CB in patients with advanced ESCC receiving anti-PD-1/PD-L1-based therapy.
    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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  • 10
    Online Resource
    Online Resource
    Frontiers Media SA ; 2019
    In:  Frontiers in Immunology Vol. 9 ( 2019-1-17)
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 9 ( 2019-1-17)
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2019
    detail.hit.zdb_id: 2606827-8
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