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This study aimed to compare the risk of developing systemic autoimmune diseases (SADs) among pediatric patients with juvenile idiopathic arthritis (JIA) treated with tumor necrosis factor inhibitors (TNFi) versus interleukin-6 inhibitors (IL-6i), based on real-world data. We conducted a retrospective real-world cohort study using the TriNetX Research Network, which contains data from over 122 million patients. Individuals ≤18 years of age with a diagnosis of JIA who initiated TNFi or IL-6i therapy between January 1, 2013, and December 31, 2024, were included. Propensity score matching (1:1) was performed to balance baseline characteristics. The primary outcome was the incidence of SADs. Hazard ratios (HRs) were estimated using Cox proportional hazards models, and subgroup and sensitivity analyses were conducted to assess robustness. After matching, 1,192 patients were included in each cohort. The TNFi group demonstrated a significantly lower incidence of SADs than the IL-6i group (17 vs. 45 events; HR = 0.37, 95% CI: 0.20-0.63). Subgroup analyses showed consistent protective effects of TNFi across age, sex, and concomitant medication strata. Sensitivity analyses across three adjusted models confirmed the robustness of the findings, yielding HRs ranging from 0.28 to 0.46. Among pediatric patients with JIA, TNF inhibitor therapy was associated with a substantially lower risk of developing systemic autoimmune diseases compared with IL-6 inhibitor therapy. These findings may inform biologic selection and long-term safety considerations in pediatric rheumatologic practice.

After the previous major dengue fever (DF) outbreaks in 2014 and 2015 in Taiwan, the second-largest DF outbreak re-emerged in 2023. A total of 178 patients with laboratory-confirmed dengue virus (DENV) infection, including 92 DENV-1 and 86 DENV-2 cases, were enrolled in this study conducted during the 2023 dengue outbreak in Kaohsiung City, Taiwan. This study aimed to analyze epidemiological characteristics, clinical severity, and risk factors for severe dengue (SD), as well as the diagnostic implications of the non-structural protein 1 (NS1) antigen rapid test. Patients infected with DENV-2 exhibited significantly older age, higher incidence of secondary infections, diabetes mellitus (DM), hypertension (HT), and longer hospital stays than patients infected with DENV-1. Multivariate analysis revealed that older age (age ≥65), secondary dengue infection, DM, and HT were significant independent predictors of SD. Compared with non-SD cases, SD patients were significantly more likely to be older (age ≥65), to exhibit a higher incidence of secondary infections and a greater prevalence of chronic diseases, including DM and HT. Notably, dengue-confirmed patients with negative NS1 results had a shorter duration since symptom onset (p < 0.001). Our DENV-1 and DENV-2 isolates are related to strains from neighboring Asian countries. Our findings emphasize the important factors of old age, secondary infections, and chronic diseases that contributed to dengue severity. We should meticulously manage these high-risk groups to prevent dengue progression. Screening incoming travelers for DF during the epidemic season will be an important measure to prevent the introduction of DENV into Taiwan.

Early diagnosis is important for the clinical management of diseases caused by dengue virus (DENV) infections. We investigated the performance of three commercially available DENV nonstructural protein 1 (NS1) rapid diagnostic tests (RDTs) using 173 acute-phase sera collected from dengue fever-suspected patients during the 2012-2013 DENV outbreak in Taiwan. The results of the NS1 RDTs were compared with those of qRT-PCR to calculate the sensitivity and specificity of the NS1 RDTs. The anti-DENV IgM and IgG RDT results were included to increase the probability of detecting acute DENV infection. The anti-DENV IgM/IgG RDT results were also compared with those of IgM/IgG captured ELISA. The sera from DENV qRT-PCR-positive patients were subjected to NS1 RDTs, as well as IgM/IgG captured ELISA. These results suggested that there was no significant difference in the sensitivities of the three commercially available DNEV NS1 RDTs; the SD NS1 RDT results showed the highest agreement with the qRT-PCR reference results, followed in order by the Bio-Rad and CTK NS1 RDT results when the specificity was considered. Inclusion of the IgM or IgG RDT results increased the likelihood of diagnosing either a primary or secondary DENV infection. NS1 RDTs were more sensitive for the detection of primary infections than secondary infections, related to DENV viremia levels determined by qRT-PCR. These results suggested that anti-DENV antibodies reduced the sensitivity of NS1 rapid tests. We also analyzed the sensitivity for the detection of different DENV serotypes, and the results suggested that the NS1 RDTs used in this study were valuable for rapid screening of acute DENV infection with DENV-1, DENV-2 and DENV-3. Our results suggest that the NS1 RDT is a good alternative to qRT-PCR analysis for timely dengue disease management and prevention in dengue-endemic regions where medical resources are lacking or during large dengue outbreaks. However, the relatively low sensitivity for DENV-4 might miss the detection of DENV-4-infected cases.

To determine the prevalence of asymptomatic dengue virus-infected blood donors during the largest dengue outbreak in Taiwan history occurred in 2015, we examined the evidence of dengue virus (DENV) infection by the detection of DENV RNA genome using real-time reverse transcription-polymerase chain reaction (real-time RT-PCR), DENV NS1 antigen using rapid diagnosis test (RDT) and anti-dengue antibody using IgM/IgG capture enzyme-linked immunosorbent assay (capture ELISA) and RDT in eight thousand serum samples from blood donations to the blood centers of the Taiwan Blood Services Foundation (TBSF) in Kaohsiung City and Tainan City during the largest dengue outbreak in Taiwan history occurred in 2015. Only one serum sample was positive for DENV RNA detection by using dengue-specific real-time RT-PCR, the virus was DENV-2 determined by serotype-specific real-time RT-PCR and sequencing, and the DENVs in the serum were confirmed as being infectious by a plaque assay. The recipient of this blood did not develop any dengue fever symptom on follow-up. None of the samples was NS1 RDT-reactive. Seventeen IgM-positive samples were identified. There was a low prevalence of asymptomatic confirmed or probable DENV-infected blood donors in our study (0.013% and 0.21%, respectively), and no symptomatic transfusion-transmitted dengue (TT dengue) was developed during the largest dengue outbreak in Taiwan history in highly endemic areas and periods.

Dengue is a global health threat, with severe cases causing significant complications. Cytokines have been proposed as potential indicators of disease severity; however, the short plasma half-life and pre-analytical instability of free-form cytokines limit their clinical applicability. Exosome-encapsulated cytokines are protected by a lipid bilayer and may provide a more stable and integrated representation of host immune responses. In this cross-sectional study, we analyzed single time-point plasma samples collected from patients during clinical evaluation between July and December 2023, with most samples obtained during the acute phase (within 7 days post-symptom onset). Plasma exosomes were isolated from patients with mild dengue, dengue with warning signs (DFWS), severe dengue (SD), other febrile illnesses, and healthy controls (HCs). Exosome-associated cytokines were quantified using a multiplex panel assessing 15 cytokines. Across the five study groups, significant differences in plasma exosome cytokine levels were observed for interleukin (IL)-1β, IL-6, IL-10, IL-12, interferon-γ (IFN-γ), and tumor necrosis factor (TNF)-α (all p < 0.05). Post-hoc analyses further demonstrated that IL-6, IL-10, and TNF-α levels were significantly higher in both the DFWS and SD groups compared with HCs (all p < 0.01). In a subsequent analysis comparing mild dengue with the combined DFWS/SD group, significantly higher exosomal levels of IL-1β, IL-5, IL-10, IL-12, IL-13, and TNF-α were observed in the DFWS/SD group (all p < 0.05). Receiver operating characteristic (ROC) analysis showed that IL-1β, IL-10, and TNF-α moderately discriminated mild from severe cases, with area under the curve (AUC) values of approximately 0.7. An \"all-positive\" panel (TNF-α, IL-10, and IL-1β) achieved 84% sensitivity and 67.5% specificity for identifying DFWS/SD. These findings suggest that combined exosomal cytokine profiling may aid in disease severity stratification. However, given the cross-sectional design and moderate discriminatory performance, larger prospective studies are needed to validate its clinical applicability.

In the current era of coronavirus disease 2019 (COVID-19), we were interested in searching for medications other than the currently available antiviral drugs Paxlovid and Molnupiravir that cause minimal side effects and do not harm the human body. Honeysuckle extract (HSE) is a traditional Chinese medicine (TCM) that has been shown to exert antiviral effects in other studies. However, no studies have indicated whether HSE has an inhibitory effect on SARS-CoV-2. We prepared HSEs from dried honeysuckle flowers. We performed a cell viability assay, median tissue culture infection dose (TCID ) assay, and qRT‒PCR, and calculated the virus titers using the Reed-Muench method to evaluate the inhibitory effects of aqueous and alcohol HSEs on SARS‒CoV‒2 and explore the possible underlying mechanisms. In this study, post-treatment with HSE resulted in dose-dependent decreases in both the RNA levels and TCID of SARS-CoV-2 in Vero E6 cells; treatment with 50 μg/ml and 100 μg/ml alcohol HSEs achieved up to 95.323% and 92.587% inhibition, respectively. Moreover, pre-treatment with aqueous HSEs effectively reduced the RNA levels, and TCID of SARS-CoV-2 by up to 99.684%, and alcohol HSEs achieved up to 99.921% inhibition; both of these effects occurred in a dose-dependent manner. The results suggest that HSEs may have the potential to prevent SARS-CoV-2 infection.

Background Dengue virus serotype 2 (DENV-2) was the major serotype in the 2015 dengue outbreak in Taiwan, while DENV-1 and DENV-3 were dominant between 2005 and 2014. We aimed to investigate whether DENV-2 contributed to disease severity and mortality in the outbreak in Kaohsiung city, Taiwan. Methods We collected serum samples from dengue patients to detect the presence of DENV and determine the serotypes by using quantitative reverse transcription-polymerase chain reaction. Our cohorts comprised 105 DENV-1-infected cases and 1,550 DENV-2-infected cases. Demographic data, DENV serotype, and comorbidities were covariates for univariate and multivariate analyses to explore the association with severity and mortality. Results The results suggested that DENV-1 persisted and circulated, while DENV-2 was dominant during the dengue outbreak that occurred between September and December 2015. However, DENV-2 did not directly contribute to either severity or mortality. Aged patients and patients with diabetes mellitus (DM) or moderate to severe chronic kidney disease (CKD) had a higher risk of developing severe dengue. The mortality of dengue patients was related to a higher Charlson comorbidity index score and severe dengue. Among DENV-2-infected patients and older patients, preexisting anti-dengue IgG, DM, and moderate to severe CKD were associated with severe dengue. Moreover, female sex and severe dengue were associated with a significantly higher risk of death. Conclusions Our findings highlight the importance of timely serological testing in elderly patients to identify potential secondary infections and focus on the meticulous management of elderly patients with DM or moderate to severe CKD to reduce dengue-related death.

Dengue fever, a mosquito-borne disease, is caused by dengue virus (DENV) which includes four major serotypes (DENV-1, -2, -3, and -4). Some serotypes cause more severe diseases than the other; severe dengue is associated with secondary infections by a different serotype. Timely serotyping can provide early warning of dengue epidemics to improve management of patients and outbreaks. A mobile insulated isothermal PCR (iiPCR) system is available to allow molecular detection of pathogens near points of need. In this study, side-by-side comparison with the CDC DENV-1-4 Real Time RT-PCR (qRT-PCR) was performed to evaluate the performance of four singleplex DENV-1-4 serotyping reverse transcription-iiPCR (RT-iiPCR) reagents for DENV subtyping on the mobile PCR system. The four RT-iiPCRs did not react with Zika virus and chikungunya virus; tests with serial dilutions of the four DENV serotypes made in human serum showed they had detection endpoints comparable to those of the reference method, indicating great analytical sensitivity and specificity. Clinical performance of the RT-iiPCR reagents was evaluated by testing 40 serum samples each (around 20 target serotype-positive and 20 DENV-negative); all four reagents had high agreement (97.5-100%) with the reference qRT-PCR. Moreover, testing of mosquitoes separately infected experimentally with each serotype showed that the four reagents detected specifically their target DENV serotypes in mosquito. With analytical and clinical performance comparable to the reference qRT-PCR assay, the four index RT-iiPCR reagents on the field-deployable PCR system can serve as a useful tool for DENV detection near points of needs.

Glioblastoma (GBM) is considered one of the most malignant, genetically heterogeneous, and therapy-resistant solid tumor. Therapeutic options are limited in GBM and involve surgical resection followed by chemotherapy and/or radiotherapy. Adjuvant therapies, including antiangiogenic treatments (AATs) targeting the VEGF–VEGFR pathway, have witnessed enhanced infiltration of bone marrow-derived myeloid cells, causing therapy resistance and tumor relapse in clinics and in preclinical models of GBM. This review article is focused on gathering previous clinical and preclinical reports featuring major challenges and lessons in GBM. Potential combination therapies targeting the tumor microenvironment (TME) to overcome the myeloid cell-mediated resistance problem in GBM are discussed. Future directions are focused on the use of TME-directed therapies in combination with standard therapy in clinical trials, and the exploration of novel therapies and GBM models for preclinical studies. We believe this review will guide the future of GBM research and therapy.

Background Dengue virus (DENV) is the leading cause of arboviral diseases in humans worldwide. Currently Dengvaxia, the first dengue vaccine licensed in 20 countries, was recommended for DENV seropositive individuals aged 9–45 years. Studying dengue seroprevalence can improve our understanding of the epidemiology and transmission dynamics of DENV, and facilitate future intervention strategies and assessment of vaccine efficacy. Several DENV envelope protein-based serological tests including IgG and IgG-capture enzyme-linked immunosorbent assays (ELISAs) have been employed in seroprevalence studies. Previously DENV IgG-capture ELISA was reported to distinguish primary and secondary DENV infections during early convalescence, however, its performance over time and in seroprevalence study remains understudied. Methods In this study, we used well-documented neutralization test- or reverse-transcription-polymerase-chain reaction-confirmed serum/plasma samples including DENV-naïve, primary and secondary DENV, primary West Nile virus, primary Zika virus, and Zika with previous DENV infection panels to compare the performance of three ELISAs. Results The sensitivity of the InBios IgG ELISA was higher than that of InBios IgG-capture and SD IgG-capture ELISAs. The sensitivity of IgG-capture ELISAs was higher for secondary than primary DENV infection panel. Within the secondary DENV infection panel, the sensitivity of InBios IgG-capture ELISA decreased from 77.8% at < 6 months to 41.7% at 1–1.5 years, 28.6% at 2–15 years and 0% at > 20 years (p < 0.001, Cochran-Armitage test for trend), whereas that of IgG ELISA remains 100%. A similar trend was observed for SD IgG-capture ELISA. Conclusions Our findings demonstrate higher sensitivity of DENV IgG ELISA than IgG-capture ELISA in seroprevalence study and interpretation of DENV IgG-capture ELISA should take sampling time and primary or secondary DENV infection into consideration.