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  • 1
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    Online Resource
    Blockade of PD-L1 Enhances Cancer Immunotherapy by Regulating Dendritic Cell Maturation and Macrophage Polarization
    MDPI AG ; 2019
    In:  Cancers Vol. 11, No. 9 ( 2019-09-19), p. 1400-
    Details
    In: Cancers, MDPI AG, Vol. 11, No. 9 ( 2019-09-19), p. 1400-
    Abstract: The immuno-inhibitory checkpoint PD-L1, regulated by tumor cells and antigen-presenting cells (APCs), dampened the activation of T cells from the PD-1/PD-L1 axis. PD-L1-expressing APCs rather than tumor cells demonstrated the essential anti-tumor effects of anti-PD-L1 monotherapy in preclinical tumor models. Using the murine tumor model, we investigated whether anti-PD-L1 antibody increased the antigen-specific immune response and anti-tumor effects induced by the antigen-specific protein vaccine, as well as the possible mechanisms regarding activation of APCs. Anti-PD-L1 antibody combined with the PEK protein vaccine generated more potent E7-specific immunity (including the number and cytotoxic activity of E7-specific cytotoxic CD8+ T lymphocytes) and anti-tumor effects than protein vaccine alone. Anti-PD-L1 antibody enhanced the maturation of dendritic cells and the proportion of M1-like macrophages in tumor-draining lymph nodes and tumors in tumor-bearing mice treated with combinatorial therapy. PD-L1 blockade overturned the immunosuppressive status of the tumor microenvironment and then enhanced the E7 tumor-specific antigen-specific immunity and anti-tumor effects generated by an E7-specific protein vaccine through modulation of APCs in an E7-expressing small tumor model. Tumor-specific antigen (like HPV E7 antigen)-specific immunotherapy combined with APC-targeting modality by PD-L1 blockade has a high translational potential in E7-specific cancer therapy.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers11091400
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2527080-1
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  • 2
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    Predicting Long-Term Prognoses and Grading Platinum Sensitivity Using a Novel Progression-Free Interval Criterion in Ovarian Clear Cell Carcinoma: A Multi-Institutional Cohort Study
    MDPI AG ; 2022
    In:  Cancers Vol. 14, No. 7 ( 2022-03-29), p. 1746-
    Details
    In: Cancers, MDPI AG, Vol. 14, No. 7 ( 2022-03-29), p. 1746-
    Abstract: This large-scale study aimed to determine the long-term influences of potential prognostic predictors and progression-free interval (PFI) criteria for grading platinum-sensitivity in ovarian clear cell carcinoma (OCCC). We retrospectively reviewed the medical records of OCCC patients presenting at nine tertiary centres (1995–2015), and evaluated patient characteristics, therapeutic factors, clinical outcomes, and hazard ratios for disease progression and death. We enrolled 536 patients (median follow-up, 36.6 months) and developed newly defined distributions of PFIs (seven and 14 months) for grading platinum sensitivity. In the multivariate model, preoperative CA125 levels and chemo-response independently predicted early-stage progression-free survival (PFS) risk. Post-progression cytoreduction correlated with reduced mortality risk. No unfavourable outcomes were observed with respect to coexisting endometriosis, fertility-sparing strategies, or platinum-based regimens. A PFI of 〈 7 months, the strongest predictor of both post-progression mortality and second relapse risks, correlated with chemo-resistance, advanced tumour stage, and shortened post-progression survival. Chemotherapy regimens commonly used in front-line or relapse settings were limited in improving prognoses, especially in the advanced-stage cohort. Clinical trials of novel targeted agents and/or innovative biomarkers for chemoresistance should be comprehensively investigated and offered early to advanced-stage patients or those with OCCC progression occurring within seven months after receiving chemotherapy.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers14071746
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527080-1
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  • 3
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    Association between Dietary Diversity Changes and Cognitive Impairment among Older People: Findings from a Nationwide Cohort Study
    MDPI AG ; 2022
    In:  Nutrients Vol. 14, No. 6 ( 2022-03-16), p. 1251-
    Details
    In: Nutrients, MDPI AG, Vol. 14, No. 6 ( 2022-03-16), p. 1251-
    Abstract: Background: Little is known about the role of dietary diversity changes in affecting cognitive function among older people. Therefore, we aimed to evaluate the associations between dietary diversity scores (DDS) changes with cognitive impairment among older adults in a large prospective cohort. Methods: Cognitive function was assessed using the Mini-Mental State Examination questionnaire at baseline and follow-up. A total of 9726 participants without Parkinson’s disease, dementia, or cognitive impairment were enrolled at baseline. Nine food groups were collected using simplified FFQ at baseline and follow-up surveys. Then nine food groups change patterns and DDS change patterns (overall, plant-based and animal-based) were assessed. The associations of above DDS changes patterns with subsequent cognitive impairment were evaluated. A multivariable-adjusted Cox proportional hazards model was used to estimate HRs and 95%CIs. Results: We documented 2805 cognitive impairments during 52,325 person-years of follow-up. Compared to high-to-high overall DDS change patterns, the multivariable adjusted HRs (95%CI) for high-to-medium, medium-to-medium, medium-to-low, low-to-medium and low-to-low DDS change patterns were 1.33 (1.12–1.57), 1.11 (0.94–1.32), 1.61 (1.39–1.86), 2.00 (1.66–2.40), 2.30 (1.90–2.78) and 2.80 (2.23–3.53), respectively. Compared with participants with stable DDS change pattern, those who in large improvement of DDS had a 13% lower risk of cognitive impairment (HRs, 0.87; 95%CI: 0.78–0.98). The associations of plant-based DDS, animal-based DDS, or nine food groups DDS change patterns with cognitive impairment were in a similar direction to the main result. Conclusions: Protective associations between maintaining high DDS and a reduced risk of cognitive impairment were observed. In contrast, lowering or maintaining a lower DDS increases the risk of cognitive impairment.
    Type of Medium: Online Resource
    ISSN: 2072-6643
    URL: Article
    DOI: 10.3390/nu14061251
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2518386-2
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  • 4
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    Age Specific Risks of Uterine Cancer in Type 2 Diabetes and Associated Comorbidities in Taiwan
    MDPI AG ; 2022
    In:  Cancers Vol. 14, No. 19 ( 2022-10-07), p. 4912-
    Details
    In: Cancers, MDPI AG, Vol. 14, No. 19 ( 2022-10-07), p. 4912-
    Abstract: Introduction: The global incidence of uterine cancer has increased substantially in recent decades. We evaluated if the trend of increasing prevalence of diabetes mellitus (DM) and obesity are attributed to the development of uterine cancer. Methods: Using data derived from the National Health Insurance database and Taiwan Cancer Registry, multivariate Cox proportional hazards regression models were adapted to analyze the risk factors of uterine cancer with potential confounding variables. Results: There were a total of 5,104,242 women aged 30–70 years enrolled in the study and 147,772 of them were diagnosed with DM during 2005–2007. In a total of 11 years of follow-up, 14,398 subjects were diagnosed with uterine cancer. An elevated risk of uterine cancer was observed in women with DM of all ages (HR 1.66, 95% CI 1.53–1.81, p 〈 0.0001). The effect of DM was highest at age 30–39 years (RR 3.05, 95% CI 2.35–3.96, p 〈 0.0001). In the group of 〈 50 years old, DM patients had at least a twofold higher risk of developing uterine cancer (HR 2.39, 95% CI 2.09–2.74, p 〈 0.0001). Subjects among all ages diagnosed with polycystic ovary syndrome (PCOS) (HR 2.91, 95% CI 2.47–3.42, p 〈 0.0001), obesity (HR 2.13, 95% CI 1.88–2.41, p 〈 0.0001), and those undergoing hormone replacement therapy (HRT) (HR 1.60, 95% CI 1.33–1.93, p 〈 0.0001) were also positively associated with uterine cancer. Positive associations of hyperlipidemia (HR 1.33, 95% CI 1.22–1.46, p 〈 0.0001) and statin use (HR 1.27, 95% CI 1.12–1.44, p = 0.0002) on uterine cancer were only observed in subjects 〈 50 years. On the contrary, hyperlipidemia was negatively associated with uterine cancer in subjects ≥50 years (HR 0.91, 95% CI: 0.84–0.98, p = 0.0122). Conclusions: DM is in general the most important risk factor for uterine cancer, especially in premenopausal women. Obesity, PCOS, HPL, statin use, and HRT were also associated with uterine cancer in subjects younger than 50 years. Premenopausal women with DM and respective comorbidities should be aware of the development of uterine cancer.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers14194912
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
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  • 5
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    Half-Metallic Property Induced by Double Exchange Interaction in the Double Perovskite Bi2BB′O6 (B, B′ = 3d Transitional Metal) via First-Principles Calculations
    MDPI AG ; 2019
    In:  Materials Vol. 12, No. 11 ( 2019-06-06), p. 1844-
    Details
    In: Materials, MDPI AG, Vol. 12, No. 11 ( 2019-06-06), p. 1844-
    Abstract: In this paper, we identify three possible candidate series of half-metals (HM) from Bi-based double perovskites Bi2BB′O6 (BB′ = transition metal ions) through calculations utilizing the density functional theory (DFT) and full-structural optimization, in which the generalized gradient approximation (GGA) and the strong correlation effect (GGA + U) are considered. After observing the candidate materials under four types of magnetic states, i.e., ferromagnetic (FM), ferrimagnetic (FiM), antiferromagnetic (AF), and nonmagnetic (NM), we found eight promising candidates for half-metallic materials. Under the GGA scheme, there are three ferromagnetic-half-metal (FM-HM) materials, Bi2CrCoO6, Bi2CrNiO6 and Bi2FeNiO6, and three FiM-HM materials, Bi2FeZnO6, Bi2CrZnO6 and Bi2CoZnO6. With implementation of the Coulomb interaction correction (GGA + U), we find two stable half-metallic materials: Bi2CrNiO6 and Bi2CrZnO6. We determine that the stability of some of these materials are tied to the double exchange interaction, an indirect interaction within the higher powers of localized spin interaction among transition metals via oxygen ions. Found in half-metallic materials, and especially those in the ferromagnetic (FM) state, the double exchange interaction is recognized in the FM-HM materials Bi2CrCoO6 and Bi2FeNiO6.
    Type of Medium: Online Resource
    ISSN: 1996-1944
    URL: Article
    DOI: 10.3390/ma12111844
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2487261-1
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  • 6
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    From Bench to Bedside: Clinical and Biomedical Investigations on Hepatitis C Virus (HCV) Genotypes and Risk Factors for Albuminuria
    MDPI AG ; 2022
    In:  Bioengineering Vol. 9, No. 10 ( 2022-09-27), p. 509-
    Details
    In: Bioengineering, MDPI AG, Vol. 9, No. 10 ( 2022-09-27), p. 509-
    Abstract: An extrahepatic manifestation of nephropathies can be a feature of the chronic hepatitis C virus (HCV) infection. Albuminuria is a major risk factor for nephropathies and chronic kidney disease (CKD). The correlation between HCV genotypes and albuminuria is still unclear. In this study, investigations have been done for the biomedical tools and methodologies used in the National Health and Nutrition Examination Survey (NHANES) public database. We searched the 2007–2016 NHANES public database to retrieve data regarding the different HCV genotypes and clinical scenarios. This study attempted to investigate the impacts of HCV genetic diversity, associated comorbidities, and racial differences on albuminuria. The urine albumin/creatinine ratio (ACR) was the primary endpoint. Among 40,856 participants, 336 participants with positive and 237 with negative HCV RNA tests were analyzed, excluding 14,454 participants with negative HCV antibodies and 25,828 which were missed. After controlling for sex, race, education level, smoking, diabetes mellitus, hepatitis B, alcohol use, and body mass index (BMI) with a generalized linear equation, HCV genotype 2 was more likely than any other genotype to cause albuminuria based on the urine ACR (p 〈 0.001). The generalized linear equation also demonstrated a significantly higher urine ACR, including hepatitis B (p 〈 0.001), diabetes mellitus (p 〈 0.001), and smoking (p = 0.026). In summary, the patients with HCV genotype 2 presented with increased albuminuria in comparison with other HCV genotypes in this 10-year retrospective analysis. HCV infection could be a risk factor of CKD; early diagnosis and appropriate treatment may improve clinical outcomes.
    Type of Medium: Online Resource
    ISSN: 2306-5354
    URL: Article
    DOI: 10.3390/bioengineering9100509
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2746191-9
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  • 7
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    Online Resource
    Dietary Diversity Changes and Cognitive Frailty in Chinese Older Adults: A Prospective Community-Based Cohort Study
    MDPI AG ; 2023
    In:  Nutrients Vol. 15, No. 17 ( 2023-08-30), p. 3784-
    Details
    In: Nutrients, MDPI AG, Vol. 15, No. 17 ( 2023-08-30), p. 3784-
    Abstract: Evidence for the effects of dietary diversity changes and cognitive frailty (CF) in the older adults is not clear. This study aimed to investigate the relationship between dietary diversity changes and CF in older adults Chinese. A total of 14,382 participants (mean age: 82.3 years) were enrolled. Dietary diversity scores (DDSs) were collected and calculated using a food frequency questionnaire. DDS changes between baseline and first follow-up were categorized into nine patterns. The associations between DDS changes and the incidence of CF were estimated using Cox proportional hazards models. During an 80,860 person-year follow-up, 3023 CF cases were identified. Groups with a decrease in DDS had increased CF risk compared with the high-to-high DDS group, with adjusted hazard ratios (HRs; 95% confidence intervals (Cis)) of 1.30 (1.06, 1.59), 2.04 (1.51, 2.74), and 1.81 (1.47, 2.22) for high-to-medium, high-to-low, and medium-to-low groups, respectively. Lower overall DDS groups were associated with greater CF risks, with HRs (95% CIs) of 1.49 (1.19, 1.86) for the low-to-medium group and 1.96 (1.53, 2.52) for the low-to-low group. Compared with the high-to-high group, significant associations with CF were found in other DDS change groups; HRs ranged from 1.38 to 3.12 for the plant-based DDS group and from 1.24 to 1.32 for the animal-based DDS group. Additionally, extreme and moderate declines in overall DDS increased CF risk compared with stable DDS, with HRs (95% CIs) of 1.67 (1.50, 1.86) and 1.13 (1.03, 1.24), respectively. In conclusion, among older adults, a declining or persistently low DDS and a moderately or extremely declining DDS were linked to higher incident CF. Plant-based DDS changes correlated more strongly with CF than animal-based DDS changes.
    Type of Medium: Online Resource
    ISSN: 2072-6643
    URL: Article
    DOI: 10.3390/nu15173784
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
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  • 8
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    Clear Cell Carcinoma of the Abdominal Wall as a Rare Complication of General Obstetric and Gynecologic Surgeries: 15 Years of Experience at a Large Academic Institution
    MDPI AG ; 2019
    In:  International Journal of Environmental Research and Public Health Vol. 16, No. 4 ( 2019-02-14), p. 552-
    Details
    In: International Journal of Environmental Research and Public Health, MDPI AG, Vol. 16, No. 4 ( 2019-02-14), p. 552-
    Abstract: The objective of this article was to report the clinicopathological characteristics, treatment modalities, and outcomes of patients with clear cell carcinoma (CCC) of the abdominal wall. Medical records of six patients diagnosed with CCC of the abdominal wall between May 2003 and May 2018 at the National Taiwan University Hospital were reviewed. All patients had prior obstetric or gynecologic surgeries. The primary clinical presentation was enlarging abdominal masses at previous surgical scars. Four patients underwent initial/primary surgeries with/without adjuvant chemotherapy. One patient received neoadjuvant chemotherapy followed by surgical intervention and adjuvant chemotherapy, the other received chemotherapy and sequential radiotherapy without any surgical intervention. Two of four patients undergoing initial/primary surgeries had disease recurrence and the remaining two cases without initial surgery experienced disease progression during primary treatment. Inguinal lymph nodes were the most frequent sites of recurrence. In conclusion, previous obstetric or gynecologic surgery can be a risk factor for CCC of the abdominal wall. Complete resection of abdominal wall tumor and suspected intra-abdominal lesions with hysterectomy and bilateral inguinal lymph nodes dissection may be the primary treatment. Adjuvant chemotherapy would be considered for potential benefits. For patients without bilateral inguinal lymph nodes dissection, careful inguinal lymph node palpation during postoperative surveillance is necessary. More cases are still needed to elucidate the clinical management of this disease.
    Type of Medium: Online Resource
    ISSN: 1660-4601
    URL: Article
    DOI: 10.3390/ijerph16040552
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2175195-X
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  • 9
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    Developing a Prognostic Gene Panel of Epithelial Ovarian Cancer Patients by a Machine Learning Model
    MDPI AG ; 2019
    In:  Cancers Vol. 11, No. 2 ( 2019-02-25), p. 270-
    Details
    In: Cancers, MDPI AG, Vol. 11, No. 2 ( 2019-02-25), p. 270-
    Abstract: Epithelial ovarian cancer patients usually relapse after primary management. We utilized the support vector machine algorithm to develop a model for the chemo-response using the Cancer Cell Line Encyclopedia (CCLE) and validated the model in The Cancer Genome Atlas (TCGA) and the GSE9891 dataset. Finally, we evaluated the feasibility of the model using ovarian cancer patients from our institute. The 10-gene predictive model demonstrated that the high response group had a longer recurrence-free survival (RFS) (log-rank test, p = 0.015 for TCGA, p = 0.013 for GSE9891 and p = 0.039 for NTUH) and overall survival (OS) (log-rank test, p = 0.002 for TCGA and p = 0.016 for NTUH). In a multivariate Cox hazard regression model, the predictive model (HR: 0.644, 95% CI: 0.436–0.952, p = 0.027) and residual tumor size 〈 1 cm (HR: 0.312, 95% CI: 0.170–0.573, p 〈 0.001) were significant factors for recurrence. The predictive model (HR: 0.511, 95% CI: 0.334–0.783, p = 0.002) and residual tumor size 〈 1 cm (HR: 0.252, 95% CI: 0.128–0.496, p 〈 0.001) were still significant factors for death. In conclusion, the patients of high response group stratified by the model had good response and favourable prognosis, whereas for the patients of medium to low response groups, introduction of other drugs or clinical trials might be beneficial.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers11020270
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2527080-1
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  • 10
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    Investigation of Neurological Complications after COVID-19 Vaccination: Report of the Clinical Scenarios and Review of the Literature
    MDPI AG ; 2023
    In:  Vaccines Vol. 11, No. 2 ( 2023-02-13), p. 425-
    Details
    In: Vaccines, MDPI AG, Vol. 11, No. 2 ( 2023-02-13), p. 425-
    Abstract: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), broke out in 2019 and became a pandemic in 2020. Since then, vaccines have been approved to prevent severe illness. However, vaccines are associated with the risk of neurological complications ranging from mild to severe. Severe complications such as vaccine-induced immune thrombotic thrombocytopenia (VITT) associated with acute ischaemic stroke have been reported as rare complications post-COVID-19 vaccination. During the pandemic era, VITT evaluation is needed in cases with a history of vaccination within the last month prior to the event. Cerebral venous sinus thrombosis (CVST) should be suspected in patients following immunization with persistent headaches who are unresponsive to analgesics. In this article, we investigated neurological complications after COVID-19 vaccination and provided more subsequent related clinical studies of accurate diagnosis, pathophysiological mechanisms, incidence, outcome, and management.
    Type of Medium: Online Resource
    ISSN: 2076-393X
    URL: Article
    DOI: 10.3390/vaccines11020425
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2703319-3
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