The Protective Effects of Influenza Vaccination in Elderly Patients with Breast Cancer in Taiwan: A Real-World Evidence-Based Study

In elderly patients with newly diagnosed breast cancer, clarity is lacking regarding the effects of influenza vaccines, particularly on clinical outcomes. This study conducted two nationwide, population-based, and propensity score-matched cohorts to estimate and compare the protective effects of influenza vaccine in elderly women and elderly patients with breast cancer. Data were derived from the National Health Insurance Research Database and Cancer Registry Database. Generalized estimating equations (GEEs) were used to compare outcomes between the vaccinated and unvaccinated cohorts. Adjusted odds ratios (aORs) were used to estimate the relative risks, and stratified analyses in the breast cancer cohort were performed to further evaluate elderly breast cancer patients undergoing a variety of adjuvant therapies. The GEE analysis showed that the aORs of death and hospitalization, including for influenza and pneumonia, respiratory diseases, respiratory failure, and heart disease, did not significantly decrease in vaccinated elderly patients with newly diagnosed breast cancer. Conversely, the aORs of all influenza-related clinical outcomes were significantly decreased in elderly women. No protective effects of influenza vaccination were found in the elderly patients with a newly diagnosed breast cancer. More studies focusing on identifying strategies to improve the real-world effectiveness of influenza vaccination to the immunocompromised are needed. Our clinical outcomes will be valuable for future public health policy establishment and shared decision making for influenza vaccine use in elderly patients with newly diagnosed breast cancer. According to our findings, regular influenza vaccine administration for elderly patients with newly diagnosed breast cancer may be reconsidered, with potential contraindications for vaccination. On the other hand, implementing the vaccination of close contacts of patients with breast cancer may be a more important strategy for enhancing protection of those fragile patients

106GBaud (200G PAM4) CWDM EML for 800G/1.6T Optical Networks and AI Applications

We report ultrahigh speed 106GBaud (200G PAM4) electro-absorption modulated laser (EML) for 800G and 1.6T optical transmission. Four CWDM EMLs of 1271, 1291, 1311 and 1331nm in 800G FR4 optical transceivers show clear eye diagram after 2km. Our 106GBaud EMLs show high bandwidth, high extinction ratio, low threshold current and high power, making it a suitable source laser for 800G/1.6T and AI applications.&nbsp

Platform Deformation Phase Correction for the AMiBA-13 Coplanar Interferometer

[[abstract]]We present a new way to solve the platform deformation problem of coplanar interferometers. The platform of a coplanar interferometer can be deformed due to driving forces and gravity. A deformed platform will induce extra components into the geometric delay of each baseline and change the phases of observed visibilities. The reconstructed images will also be diluted due to the errors of the phases. The platform deformations of The Yuan-Tseh Lee Array for Microwave Background Anisotropy (AMiBA) were modeled based on photogrammetry data with about 20 mount pointing positions. We then used the differential optical pointing error between two optical telescopes to fit the model parameters in the entire horizontal coordinate space. With the platform deformation model, we can predict the errors of the geometric phase delays due to platform deformation with a given azimuth and elevation of the targets and calibrators. After correcting the phases of the radio point sources in the AMiBA interferometric data, we recover 50%-70% flux loss due to phase errors. This allows us to restore more than 90% of a source flux. The method outlined in this work is not only applicable to the correction of deformation for other coplanar telescopes but also to single-dish telescopes with deformation problems. This work also forms the basis of the upcoming science results of AMiBA-13.[[notice]]補正完畢[[journaltype]]國外[[incitationindex]]SCI[[ispeerreviewed]]Y[[booktype]]電子版[[booktype]]紙本[[countrycodes]]US

High myopia at high altitudes

Background: Optic nerve sheath diameter (ONSD) increases significantly at high altitudes, and is associated with the presence and severity of acute mountain sickness (AMS). Exposure to hypobaria, hypoxia, and coldness when hiking also impacts intraocular pressure (IOP). To date, little is known about ocular physiological responses in trekkers with myopia at high altitudes. This study aimed to determine changes in the ONSD and IOP between participants with and without high myopia (HM) during hiking and to test whether these changes could predict symptoms of AMS.Methods: Nine participants with HM and 18 without HM participated in a 3-day trek of Xue Mountain. The ONSD, IOP, and questionnaires were examined before and during the trek of Xue Mountain.Results: The ONSD values increased significantly in both HM (p = 0.005) and non-HM trekkers (p = 0.018) at an altitude of 1,700 m. In the HM group, IOP levels were greater than those in the non-HM group (p = 0.034) on the first day of trekking (altitude: 3,150 m). No statistically significant difference was observed between the two groups for the values of ONSD. Fractional changes in ONSD at an altitude of 1,700 m were related to the development of AMS (rpb = 0.448, p = 0.019) and the presence of headache symptoms (rpb = 0.542, p = 0.004). The area under the ROC curve for the diagnostic performance of ONSD fractional changes at an altitude of 1,700 m was 0.859 for predicting the development of AMS and 0.803 for predicting the presence of headache symptoms.Conclusion: Analysis of changes in ONSD at moderate altitude could predict AMS symptoms before an ascent to high altitude. Myopia may impact physiological accommodation at high altitudes, and HM trekkers potentially demonstrate suboptimal regulation of aqueous humor in such environments

Small-Molecule Synthetic Compound Norcantharidin Reverses Multi-Drug Resistance by Regulating Sonic Hedgehog Signaling in Human Breast Cancer Cells

Multi-drug resistance (MDR), an unfavorable factor compromising treatment efficacy of anticancer drugs, involves upregulated ATP binding cassette (ABC) transporters and activated Sonic hedgehog (Shh) signaling. By preparing human breast cancer MCF-7 cells resistant to doxorubicin (DOX), we examined the effect and mechanism of norcantharidin (NCTD), a small-molecule synthetic compound, on reversing multidrug resistance. The DOX-prepared MCF-7R cells also possessed resistance to vinorelbine, characteristic of MDR. At suboptimal concentration, NCTD significantly inhibited the viability of DOX-sensitive (MCF-7S) and DOX-resistant (MCF-7R) cells and reversed the resistance to DOX and vinorelbine. NCTD increased the intracellular accumulation of DOX in MCF-7R cells and suppressed the upregulated the mdr-1 mRNA, P-gp and BCRP protein expression, but not the MRP-1. The role of P-gp was strengthened by partial reversal of the DOX and vinorelbine resistance by cyclosporine A. NCTD treatment suppressed the upregulation of Shh expression and nuclear translocation of Gli-1, a hallmark of Shh signaling activation in the resistant clone. Furthermore, the Shh ligand upregulated the expression of P-gp and attenuated the growth inhibitory effect of NCTD. The knockdown of mdr-1 mRNA had not altered the expression of Shh and Smoothened in both MCF-7S and MCF-7R cells. This indicates that the role of Shh signaling in MDR might be upstream to mdr-1/P-gp, and similar effect was shown in breast cancer MDA-MB-231 and BT-474 cells. This study demonstrated that NCTD may overcome multidrug resistance through inhibiting Shh signaling and expression of its downstream mdr-1/P-gp expression in human breast cancer cells

A Subset of Latency-Reversing Agents Expose HIV-Infected Resting CD4⁺ T-Cells to Recognition by Cytotoxic T-Lymphocytes

Resting CD4⁺ T-cells harboring inducible HIV proviruses are a critical reservoir in antiretroviral therapy (ART)-treated subjects. These cells express little to no viral protein, and thus neither die by viral cytopathic effects, nor are efficiently cleared by immune effectors. Elimination of this reservoir is theoretically possible by combining latency-reversing agents (LRAs) with immune effectors, such as CD8⁺ T-cells. However, the relative efficacy of different LRAs in sensitizing latently-infected cells for recognition by HIV-specific CD8⁺ T-cells has not been determined. To address this, we developed an assay that utilizes HIV-specific CD8⁺ T-cell clones as biosensors for HIV antigen expression. By testing multiple CD8⁺ T-cell clones against a primary cell model of HIV latency, we identified several single agents that primed latently-infected cells for CD8⁺ T-cell recognition, including IL-2, IL-15, two IL-15 superagonists (IL-15SA and ALT-803), prostratin, and the TLR-2 ligand Pam₃CSK₄. In contrast, we did not observe CD8⁺ T-cell recognition of target cells following treatment with histone deacetylase inhibitors or with hexamethylene bisacetamide (HMBA). In further experiments we demonstrate that a clinically achievable concentration of the IL-15 superagonist ‘ALT-803’, an agent presently in clinical trials for solid and hematological tumors, primes the natural ex vivo reservoir for CD8⁺ T-cell recognition. Thus, our results establish a novel experimental approach for comparative evaluation of LRAs, and highlight ALT-803 as an LRA with the potential to synergize with CD8⁺ T-cells in HIV eradication strategies.United States. National Institutes of Health (AI111860

T-cell responses targeting HIV Nef uniquely correlate with infected cell frequencies after long-term antiretroviral therapy

HIV-specific CD8+ T-cell responses limit viral replication in untreated infection. After the initiation of antiretroviral therapy (ART), these responses decay and the infected cell population that remains is commonly considered to be invisible to T-cells. We hypothesized that HIV antigen recognition may persist in ART-treated individuals due to low-level or episodic protein expression. We posited that if persistent recognition were occurring it would be preferentially directed against the early HIV gene products Nef, Tat, and Rev as compared to late gene products, such as Gag, Pol, and Env, which have higher barriers to expression. Using a primary cell model of latency, we observed that a Nef-specific CD8+ T-cell clone exhibited low-level recognition of infected cells prior to reactivation and robust recognition shortly thereafter. A Gag-specific CD8+ T-cell clone failed to recognized infected cells under these conditions, corresponding with a lack of detectable Gag expression. We measured HIV-specific T-cell responses in 96 individuals who had been suppressed on ART for a median of 7 years, and observed a significant, direct correlation between cell-associated HIV DNA levels and magnitudes of IFN-γ-producing Nef/Tat/Rev-specific T-cell responses. This correlation was confirmed in an independent cohort (n = 18). Correlations were not detected between measures of HIV persistence and T-cell responses to other HIV antigens. The correlation with Nef/Tat/Rev-specific T-cells was attributable to Nef-specific responses, the breadth of which also correlated with HIV DNA levels. These results suggest that ongoing Nef expression in ART-treated individuals drives preferential maintenance and/or expansion of T-cells reactive to this protein, implying sensing of infected cells by the immune system. The direct correlation, however, suggests that recognition does not result in efficient elimination of infected cells. These results raise the possibility that enhancing the cytolytic activity of Nef-specific T-cells may lead to reductions in infected cell frequencies, even in the absence of therapeutic latency reversal

Dengue Meteorological Determinants during Epidemic and Non-Epidemic Periods in Taiwan

The identification of the key factors influencing dengue occurrence is critical for a successful response to the outbreak. It was interesting to consider possible differences in meteorological factors affecting dengue incidence during epidemic and non-epidemic periods. In this study, the overall correlation between weekly dengue incidence rates and meteorological variables were conducted in southern Taiwan (Tainan and Kaohsiung cities) from 2007 to 2017. The lagged-time Poisson regression analysis based on generalized estimating equation (GEE) was also performed. This study found that the best-fitting Poisson models with the smallest QICu values to characterize the relationships between dengue fever cases and meteorological factors in Tainan (QICu = −8.49 × 10−3) and Kaohsiung (−3116.30) for epidemic periods, respectively. During dengue epidemics, the maximum temperature with 2-month lag (β = 0.8400, p < 0.001) and minimum temperature with 5-month lag (0.3832, p < 0.001). During non-epidemic periods, the minimum temperature with 3-month lag (0.1737, p < 0.001) and mean temperature with 2-month lag (2.6743, p < 0.001) had a positive effect on dengue incidence in Tainan and Kaohsiung, respectively

我國禁止行賄外國公務員法制之探討 Reviewing Anti-Bribery Law on Combating Bribery of Foreign Public Officials

近年有關禁止行賄外國公務員之議題已受到國際社會重視，尤其當美國政府對於違反海外反貪腐法（Foreign Corrupt Practices Act, FCPA）之執法地域範圍從歐美擴及於亞洲時，我國企業及科技公司應更加重視企業行賄外國公務員之防制，以降低相關法律風險。然而，過去我國肅貪政策係以公部門貪腐防制為重心。雖然我國於 2003 年將行賄外國公務員行為刑罰化，惟從防制跨國賄賂犯罪與提升企業競爭力之角度而言，現行法存有許多疑義尚待釐清，並使得我國企業無妥適之法律制度可資遵循。本文旨在探討我國禁止行賄外國公務員規範與實務之相關問題，除說明有關 FCPA 之企業遵法議題外，並嘗試從美國法觀點與實證質性研究分析我國防制行賄外國公務員及企業遵法應有之制度內涵，以及提出立法政策建議，以兼顧打擊跨國行賄與保障企業利益之目的。 In recent years, anti-bribery of foreign public officials has received high attention by the international community. While the U.S. government expands the enforcement region of the Foreign Corrupt Practices Act (FCPA) from Europe and America to Asia, the enterprises and technology industries in Taiwan should pay more attention to the prohibition against bribing foreign officials in order to decrease legal risk. In the past, the main regulate focus of the corruption prohibition laws in Taiwan were mainly on the public sector. Although the bribery of foreign officials became criminalized in Taiwan in 2003, from the perspective of implementing the anti-bribery policy and enhancing the competitiveness edge of the enterprises, the laws currently in force leave many problems to be solved, and the enterprises was left no clear rules to comply. For the first part of this article, it will introduce the issues currently existed in the anti-bribery laws in Taiwan. In the sec-ond part, this article will clarify the recent issues regarding the corporate compliance program of the FCPA. Finally, it will consider and provide legislative suggestions that may improve Taiwan’s anti-bribery policy from the perspective of U.S. law and on the basis of qualitative research conducted

Treatment patterns of targeted and nontargeted therapies and survival effects in patients with locally advanced head and neck cancer in Taiwan

Abstract Background Taiwan’s National Health Insurance has covered targeted therapy, namely cetuximab, for locally advanced head and neck cancers (LAHNC) since July 2009. This study examines treatment trends and survival effects of locally advanced head and neck cancer patients before and after Taiwan’s National Health Insurance covered cetuximab. Methods We examined treatment trends and survival effects for patients with LAHNC using Taiwan’s National Health Insurance Research Database. Patients who received treatment within 6 months were categorized as either nontargeted or targeted therapy groups. We analyzed treatment trends with the Cochran-Armitage trend test and explored factors associated with treatment selection and survival effects using multivariable logistic regression and Cox proportional hazards models. Results Of the 20,900 LAHNC patients included in the study, 19,696 received nontargeted therapy, while 1,204 received targeted therapy. Older patients with more comorbid conditions, advanced stages and patients with hypopharynx and oropharynx cancers were more likely to receive targeted therapy with concomitant cetuximab treatment. Patients who received targeted therapy in addition to other treatment modalities had a greater risk of one-year and long-term all-cause mortality or cancer-specific mortality than those without receiving targeted therapy (P < 0.001). Conclusions Our study found an increasing trend in cetuximab utilization among LAHNC after reimbursement in Taiwan, but overall usage rates were low. LAHNC patients receiving cetuximab with other treatments had higher mortality risk than those receiving cisplatin, suggesting cisplatin may be preferred. Further research is needed to identify subgroups that could benefit from concomitant cetuximab treatment