Politics matters for individual attitudes toward vaccine donation: cross-national evidence from the United States and Taiwan.

BACKGROUND: Vaccine equity has been a major concern during the COVID-19 pandemic. According to the principle of vaccine equity, donor countries should apply the criterion of needs to make decisions about vaccine donation instead of considering recipient countries' economic status. We examine whether people follow the same criterion or consider other factors to decide which country to donate vaccines and how many vaccines should be delivered. METHODS: We conducted online surveys with the design of conjoint experiment in the United States and Taiwan in 2021. 1,532 American citizens and 1,587 Taiwanese citizens were interviewed. The respondents were broadly quota-matched to their respective demographic proportions on the dimensions of age, gender, and education. We estimated the average marginal component effects (AMCEs) of the conjoint attributes by using the OLS regression models with standard errors clustered at the respondent level. RESULTS: 15,320 and 15,870 decisions on vaccine donation generated by conjoint experiment respectively in the United States and Taiwan were included in the analysis. Both American and Taiwanese people tend to donate vaccines to countries that suffer severe consequences of COVID-19 and democracies compared to authoritarian countries. However, they are less willing to donate vaccines to those with higher levels of capability in response to COVID-19. Taiwanese people tend to donate vaccines to countries having formal diplomatic relations with Taiwan (AMCE 13.4%, 95% CI 11.8%-15.1%). Nonetheless, American people would rather donate vaccines to countries without formal diplomatic relations with the United States (AMCE - 4.0%, 95% CI -5.6%--2.4%). CONCLUSIONS: The findings reveal that politics plays a significant role in people's decisions about vaccine donation. Under electoral pressure, political leaders must think about how to respond to the public's preferences over vaccine donation to achieve vaccine equity and address the global health crisis.

BiTE-Secreting CAR-γδT as a Dual Targeting Strategy for the Treatment of Solid Tumors.

HLA-G is considered as an immune checkpoint protein and a tumor-associated antigen. In the previous work, it is reported that CAR-NK targeting of HLA-G can be used to treat certain solid tumors. However, the frequent co-expression of PD-L1 and HLA-G) and up-regulation of PD-L1 after adoptive immunotherapy may decrease the effectiveness of HLA-G-CAR. Therefore, simultaneous targeting of HLA-G and PD-L1 by multi-specific CAR could represent an appropriate solution. Furthermore, gamma-delta T (γδT) cells exhibit MHC-independent cytotoxicity against tumor cells and possess allogeneic potential. The utilization of nanobodies offers flexibility for CAR engineering and the ability to recognize novel epitopes. In this study, Vδ2 γδT cells are used as effector cells and electroporated with an mRNA-driven, nanobody-based HLA-G-CAR with a secreted PD-L1/CD3ε Bispecific T-cell engager (BiTE) construct (Nb-CAR.BiTE). Both in vivo and in vitro experiments reveal that the Nb-CAR.BiTE-γδT cells could effectively eliminate PD-L1 and/or HLA-G-positive solid tumors. The secreted PD-L1/CD3ε Nb-BiTE can not only redirect Nb-CAR-γδT but also recruit un-transduced bystander T cells against tumor cells expressing PD-L1, thereby enhancing the activity of Nb-CAR-γδT therapy. Furthermore, evidence is provided that Nb-CAR.BiTE redirectes γδT into tumor-implanted tissues and that the secreted Nb-BiTE is restricted to the tumor site without apparent toxicity.

CAR-T cells targeting HLA-G as potent therapeutic strategy for EGFR-mutated and overexpressed oral cancer.

Oral squamous cell carcinoma (OSCC) is a common malignancy in the world. Recently, scientists have focused on therapeutic strategies to determine the regulation of tumors and design molecules for specific targets. Some studies have demonstrated the clinical significance of human leukocyte antigen G (HLA-G) in malignancy and NLR family pyrin domain-containing 3 (NLRP3) inflammasome in promoting tumorigenesis in OSCC. This is the first study to investigate whether aberrant epidermal growth factor receptor (EGFR) induces HLA-G expression through NLRP3 inflammasome-mediated IL-1ß secretion in OSCC. Our results showed that the upregulation of NLRP3 inflammasome leads to abundant HLA-G in the cytoplasm and cell membrane of FaDu cells. In addition, we also generated anti-HLA-G chimeric antigen receptor (CAR)-T cells and provided evidence for their effects in EGFR-mutated and overexpressed oral cancer. Our results may be integrated with OSCC patient data to translate basic research into clinical significance and may lead to novel EGFR-aberrant OSCC treatment.

Regulation of Aqueous Humor Secretion by Melatonin in Porcine Ciliary Epithelium.

Secretion of melatonin, a natural hormone whose receptors are present in the ciliary epithelium, displays diurnal variation in the aqueous humor (AH), potentially contributing to the regulation of intraocular pressure. This study aimed to determine the effects of melatonin on AH secretion in porcine ciliary epithelium. The addition of 100 µM melatonin to both sides of the epithelium significantly increased the short-circuit current (Isc) by ~40%. Stromal administration alone had no effect on the Isc, but aqueous application triggered a 40% increase in Isc, similar to that of bilateral application without additive effect. Pre-treatment with niflumic acid abolished melatonin-induced Isc stimulation. More importantly, melatonin stimulated the fluid secretion across the intact ciliary epithelium by ~80% and elicited a sustained increase (~50-60%) in gap junctional permeability between pigmented ciliary epithelial (PE) cells and non-pigmented ciliary epithelial (NPE) cells. The expression of MT3 receptor was found to be >10-fold higher than that of MT1 and MT2 in porcine ciliary epithelium. Aqueous pre-treatment with MT1/MT2 antagonist luzindole failed to inhibit the melatonin-induced Isc response, while MT3 antagonist prazosin pre-treatment abolished the Isc stimulation. We conclude that melatonin facilitates Cl- and fluid movement from PE to NPE cells, thereby stimulating AH secretion via NPE-cell MT3 receptors.

Role of air pollutants in dengue fever incidence: evidence from two southern cities in Taiwan.

Air pollution may be involved in spreading dengue fever (DF) besides rainfalls and warmer temperatures. While particulate matter (PM), especially those with diameter of 10 µm (PM10) or 2.5 µm or less (PM25), and NO2 increase the risk of coronavirus 2 infection, their roles in triggering DF remain unclear. We explored if air pollution factors predict DF incidence in addition to the classic climate factors. Public databases and DF records of two southern cities in Taiwan were used in regression analyses. Month order, PM10 minimum, PM2.5 minimum, and precipitation days were retained in the enter mode model, and SO2 minimum, O3 maximum, and CO minimum were retained in the stepwise forward mode model in addition to month order, PM10 minimum, PM2.5 minimum, and precipitation days. While PM2.5 minimum showed a negative contribution to the monthly DF incidence, other variables showed the opposite effects. The sustain of month order, PM10 minimum, PM2.5 minimum, and precipitation days in both regression models confirms the role of classic climate factors and illustrates a potential biological role of the air pollutants in the life cycle of mosquito vectors and dengue virus and possibly human immune status. Future DF prevention should concern the contribution of air pollution besides the classic climate factors.

Infection Patterns of a Liberibacter Associated with Macrohomotoma gladiata, a Psyllid Feeding on Ficus microcarpa.

Almost all known Liberibacters can be transmitted by psyllids. This suggests that there is a coevolutionary relationship between these two groups of organisms. However, detailed investigation of Liberibacters and psyllids have often focused on only a few species, thus potentially limiting knowledge on Liberibacter-psyllid associations. This study investigated the infection patterns of a Liberibacter inhabiting Macrohomotoma gladiata, a psyllid species feeding on Ficus microcarpa. Comparison of the Liberibacter's near-full-length 16S rDNA sequence with those of other known Liberibacters revealed that it is closely related to Candidatus Liberibacter asiaticus. A survey of different M. gladiata populations in Taiwan using conventional and quantitative PCR (qPCR) indicated that the Liberibacter could be detected with variable frequencies in all the tested populations; the proportions of individuals carrying large Liberibacter populations also differed depending on the population. Additional analysis of a larger set of samples collected from one specific population revealed that the psyllid's gender and abdominal color were associated with Liberibacter infection density. Significantly greater proportions of individuals with a blue/green abdomen carried high Liberibacter titers. Analysis of the psyllids' body lengths revealed that body size was not affected by Liberibacter infection status and that females, particularly those with an orange abdomen, tended to be larger. The infection patterns of Liberibacter in nymph-infested and nymph-free twigs of F. microcarpa were also determined, and Liberibacter distribution was found to be associated with the presence of nymphs. These findings broaden the understanding of Liberibacter ecology in general and have implications for managing Liberibacter-associated diseases. IMPORTANCE Despite the ever-increasing interest in Liberibacter-psyllid interactions, most of the current knowledge on the subject has been established from studies focusing on species associated with crop diseases. To obtain a more holistic understanding of Liberibacter ecology, we investigated the infection patterns of a Liberibacter recently detected in Macrohomotoma gladiata, a psyllid pest of Ficus microcarpa. We showed that a Liberibacter closely related to Candidatus Liberibacter asiaticus is widely distributed across M. gladiata populations in Taiwan. The study also identified factors associated with the Liberibacter infection patterns, both in M. gladiata and in F. microcarpa. The effects of Liberibacter infection status on psyllid body sizes were also examined. Some of the patterns detected in this work were similar those found in well-known Liberibacters, while some were the opposite. The findings in this work broaden our understanding of Liberibacter ecology in general and may facilitate development of strategies for managing plant diseases.

Intraoperative Needle Tip Tracking with an Integrated Fibre-Optic Ultrasound Sensor.

Ultrasound is an essential tool for guidance of many minimally-invasive surgical and interventional procedures, where accurate placement of the interventional device is critical to avoid adverse events. Needle insertion procedures for anaesthesia, fetal medicine and tumour biopsy are commonly ultrasound-guided, and misplacement of the needle may lead to complications such as nerve damage, organ injury or pregnancy loss. Clear visibility of the needle tip is therefore critical, but visibility is often precluded by tissue heterogeneities or specular reflections from the needle shaft. This paper presents the in vitro and ex vivo accuracy of a new, real-time, ultrasound needle tip tracking system for guidance of fetal interventions. A fibre-optic, Fabry-Pérot interferometer hydrophone is integrated into an intraoperative needle and used to localise the needle tip within a handheld ultrasound field. While previous, related work has been based on research ultrasound systems with bespoke transmission sequences, the new system-developed under the ISO 13485 Medical Devices quality standard-operates as an adjunct to a commercial ultrasound imaging system and therefore provides the image quality expected in the clinic, superimposing a cross-hair onto the ultrasound image at the needle tip position. Tracking accuracy was determined by translating the needle tip to 356 known positions in the ultrasound field of view in a tank of water, and by comparison to manual labelling of the the position of the needle in B-mode US images during an insertion into an ex vivo phantom. In water, the mean distance between tracked and true positions was 0.7 ± 0.4 mm with a mean repeatability of 0.3 ± 0.2 mm. In the tissue phantom, the mean distance between tracked and labelled positions was 1.1 ± 0.7 mm. Tracking performance was found to be independent of needle angle. The study demonstrates the performance and clinical compatibility of ultrasound needle tracking, an essential step towards a first-in-human study.

PM2.5 exposure and risk of lung adenocarcinoma in women of Taiwan: A case-control study with density sampling.

BACKGROUND AND OBJECTIVE: The prevalence of smoking among women in Taiwan is <5%, but the incidence of lung cancer remains high. This study determined the association between PM2.5 (fine particulate matter with an aerodynamic diameter of ≤2.5 µm) exposure and lung cancer among women in Taiwan. METHODS: In total, 21,301 female lung cancer cases nationwide were newly diagnosed between 2012 and 2017. Each case was age-, sex- and calendar year-matched with four controls randomly selected from the general population. Allowing a latent period of 5 years, we estimated the PM2.5 and nitrogen dioxide (NO2 ) exposures for each individual according to the residential changes from 2000. We adopted self-reported smoking statuses for the cases, while those of controls were estimated using annual surveys in each residential county. We performed multiple logistic regression analyses to examine the associations between PM2.5 and NO2 exposures and incident lung cancer cases. RESULTS: The ORs of lung adenocarcinoma for the third (30.5-35.1 µg/m3 ), fourth (35.1-39.3 µg/m3 ) and fifth PM2.5 exposure quintiles (39.3-48.1 µg/m3 ) relative to the first quintile were 1.10 (95% CI: 1.04-1.16), 1.12 (95% CI: 1.06-1.19) and 1.10 (95% CI: 1.04-1.16), respectively, after adjusting for smoking, residence and comorbidities. A dose-response relationship (p = 0.004) was found. The associations persisted with a 10-year latency and were not detected for small-cell and squamous cell carcinoma after control for smoking. We did not observe a similar effect for NO2 exposure. CONCLUSION: Residential PM2.5 exposure higher than 30 µg/m3 was associated with an increased risk of lung adenocarcinoma in women of Taiwan.

Intelligent Healthcare System Using Patients Confidential Data Communication in Electrocardiogram Signals.

With the advent of the aging era, healthcare and elderly care have become the focus of medical care, especially the care of the elderly with dementia. Patients' confidential data hiding is a useful technology for healthcare and patient information privacy. In this study, we implement an intelligent healthcare system using the multiple-coefficient quantization technology in transform domain to hide patients' confidential data into electrocardiogram (ECG) signals obtained by ECG sensor module. In embedding patients' confidential data, we first consider a non-linear model for optimizing the quality of the embedded ECG signals. Next, we apply simulated annealing (SA) to solve the non-linear model so as to have good signal-to-noise ratio (SNR), root mean square error (RMSE), and relative RMSE (rRMSE). Accordingly, the distortion of the PQRST complexes and the ECG amplitude is very small so that the embedded confidential data can satisfy the requirements of physiological diagnostics. In end devices, one can receive the ECG signals with the embedded confidential data and without the original ECG signals. Experimental results confirm the effectiveness of our method, which remains high quality for each ECG signal with the embedded confidential data no matter how the quantization size Q is increased.

The role of urease in the acid stress response and fimbriae expression in Klebsiella pneumoniae CG43.

BACKGROUND/PURPOSE: Two urease operons were identified in Klebsiella pneumoniae CG43, ure-1 and ure-2. This study investigates whether a differential regulation of the expression of ure-1 and ure-2 exists and how urease activity influences the acid stress response and expression of type 1 and type 3 fimbriae. METHODS: The ureA1 and ureA2 gene specific deletion mutants were constructed. Promoter activity was assessed using a LacZ reporter system. The sensitivity to acid stress was determined by assessing the survival after pH 2.5 treatment. The influence on type 1 and type 3 fimbriae expression was assessed using western blotting and mannose-sensitive yeast agglutination and biofilm formation assay, respectively. RESULTS: Bacterial growth analysis in mM9-U or modified Stuart broth revealed that ure-1 was the principal urease system, and ure-2 had a negative effect on ure-1 activity. Deletion of the fur or nac gene had no apparent effect on the activity of Pure1, Pure2-1, and Pure2-2. The Pure2-2 activity was enhanced by deletion of the hns gene. ureA1 deletion increased acid stress sensitivity, whereas the deleting effect of ureA2 was notable without hns. Deletion of ureA1 or ureA2 significantly induced the expression of type 1 fimbriae but decreased MrkA production and biofilm formation. CONCLUSION: ure-1 is the primary expression system in K. pneumoniae CG43, while ure-2 is active in the absence of hns. Impairment of urease activity increases the sensitivity to acid stress, and the accumulation of urea induces the expression of type 1 fimbriae but represses type 3 fimbriae expression.

Neutral Nonenzymatic Glucose Biosensors Based on Electrochemically Deposited Pt/Au Nanoalloy Electrodes.

BACKGROUND: Type I diabetes occurs when the pancreas can only make limited or minimal insulin. Patients with type 1 diabetes need effective approaches to manage diabetes and maintain their blood-glucose concentration. Recently, continuous glucose monitoring (CGM) has been used to help control blood-glucose levels in patients with type 1 diabetes. Patients with type 2 diabetes may also benefit from CGM on multiple insulin injections, basal insulin, or sulfonylureas. Enzyme-free glucose detection in a neutral environment is the recent development trend of CGM. MATERIALS AND METHODS: Pt/Au alloy electrodes for enzyme-free glucose detection in a neutral environment were formed by electrochemically depositing Pt/Au alloy on a thin polycarbonate (PC) membrane surface with a uniformly distributed micro-hemisphere array. The PC membranes were fabricated using semiconductor microelectromechanical manufacturing processes, precision micro-molding, and hot embossing. Amperometry was used to measure the glucose concentration in PBS (pH 7.4) and artificial human serum. RESULTS: The Pt/Au nanoalloy electrode had excellent specificity for glucose detection, according to the experimental results. The device had a sensitivity of 2.82 µA mM-1 cm-2, a linear range of 1.39-13.9 mM, and a detection limit of 0.482 mM. Even though the complex interfering species in human blood can degrade the sensing signal, further experiments conducted in artificial serum confirmed the feasibility of the proposed Pt/Au nanoalloy electrode in clinical applications. CONCLUSION: The proposed Pt/Au nanoalloy electrode can catalyze glucose reactions in neutral solutions with enhancing sensing performance by the synergistic effect of bimetallic materials and increasing detection surface area. This novel glucose biosensor has advantages, such as technology foresight, good detection performance, and high mass production feasibility. Thus, the proposed neutral nonenzymatic glucose sensor can be further used in CGMs.

Species-Specific Endotoxin Stimulus Determines Toll-Like Receptor 4- and Caspase 11-Mediated Pathway Activation Characteristics.

The innate immune system is the body's first line of defense against pathogens and its protection against infectious diseases. On the surface of host myeloid cells, Toll-like receptor 4 (TLR4) senses lipopolysaccharide (LPS), the major outer membrane component of Gram-negative bacteria. Intracellularly, LPS is recognized by caspase 11 through the noncanonical inflammasome to induce pyroptosis-an inflammatory form of lytic cell death. While TLR4-mediated signaling perturbations result in secretion of cytokines and chemokines that help clear infection and facilitate adaptive immunity, caspase 11-mediated pyroptosis leads to the release of damage-associated molecular patterns and inflammatory mediators. Although the core signaling events and many associated proteins in the TLR4 signaling pathway are known, the complex signaling events and protein networks within the noncanonical inflammasome pathway remain obscure. Moreover, there is mounting evidence for pathogen-specific innate immune tuning. We characterized the major LPS structures from two different pathogens, modeled their binding to the surface receptors, systematically examined macrophage inflammatory responses to these LPS molecules, and surveyed the temporal differences in global protein secretion resulting from TLR4 and caspase 11 activation in macrophages using mass spectrometry (MS)-based quantitative proteomics. This integrated strategy, spanning functional activity assays, top-down structural elucidation of endotoxins, and secretome analysis of stimulated macrophages, allowed us to identify crucial differences in TLR4- and caspase 11-mediated protein secretion in response to two Gram-negative bacterial endotoxins. IMPORTANCE Macrophages and monocytes are innate immune cells playing an important role in orchestrating the initial innate immune response to bacterial infection and the tissue damage. This response is facilitated by specific receptors on the cell surface and intracellularly. One of the bacterial molecules recognized is a Gram-negative bacteria cell wall component, lipopolysaccharide (LPS). The structure of LPS differs between different species. We have characterized the innate immune responses to the LPS molecules from two bacteria, Escherichia coli and Bordetella pertussis, administered either extracellularly or intracellularly, whose structures we first determined. We observed marked differences in the temporal dynamics and amounts of proteins secreted by the innate immune cells stimulated by any of these molecules and routes. This suggests that there is specificity in the first line of response to different Gram-negative bacteria that can be explored to tailor specific therapeutic interventions.

Lead compounds for the development of SARS-CoV-2 3CL protease inhibitors.

We report the identification of three structurally diverse compounds - compound 4, GC376, and MAC-5576 - as inhibitors of the SARS-CoV-2 3CL protease. Structures of each of these compounds in complex with the protease revealed strategies for further development, as well as general principles for designing SARS-CoV-2 3CL protease inhibitors. These compounds may therefore serve as leads for the basis of building effective SARS-CoV-2 3CL protease inhibitors.

Inhibitors of Coronavirus 3CL Proteases Protect Cells from Protease-Mediated Cytotoxicity.

We describe a mammalian cell-based assay to identify coronavirus 3CL protease (3CLpro) inhibitors. This assay is based on rescuing protease-mediated cytotoxicity and does not require live virus. By enabling the facile testing of compounds across a range of 15 distantly related coronavirus 3CLpro enzymes, we identified compounds with broad 3CLpro-inhibitory activity. We also adapted the assay for use in compound screening and in doing so uncovered additional severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3CLpro inhibitors. We observed strong concordance between data emerging from this assay and those obtained from live-virus testing. The reported approach democratizes the testing of 3CLpro inhibitors by developing a simplified method for identifying coronavirus 3CLpro inhibitors that can be used by the majority of laboratories, rather than the few with extensive biosafety infrastructure. We identified two lead compounds, GC376 and compound 4, with broad activity against all 3CL proteases tested, including 3CLpro enzymes from understudied zoonotic coronaviruses. IMPORTANCE Multiple coronavirus pandemics have occurred over the last 2 decades. This has highlighted a need to be proactive in the development of therapeutics that can be readily deployed in the case of future coronavirus pandemics. We developed and validated a simplified cell-based assay for the identification of chemical inhibitors of 3CL proteases encoded by a wide range of coronaviruses. This assay is reporter free, does not require specialized biocontainment, and is optimized for performance in high-throughput screening. By testing reported 3CL protease inhibitors against a large collection of 3CL proteases with variable sequence similarity, we identified compounds with broad activity against 3CL proteases and uncovered structural insights into features that contribute to their broad activity. Furthermore, we demonstrated that this assay is suitable for identifying chemical inhibitors of proteases from families other than 3CL proteases.

Potential of Magnetic Hyperthermia to Stimulate Localized Immune Activation.

Magnetic hyperthermia (MH) harnesses the heat-releasing properties of superparamagnetic iron oxide nanoparticles (SPIONs) and has potential to stimulate immune activation in the tumor microenvironment whilst sparing surrounding normal tissues. To assess feasibility of localized MH in vivo, SPIONs are injected intratumorally and their fate tracked by Zirconium-89-positron emission tomography, histological analysis, and electron microscopy. Experiments show that an average of 49% (21-87%, n = 9) of SPIONs are retained within the tumor or immediately surrounding tissue. In situ heating is subsequently generated by exposure to an externally applied alternating magnetic field and monitored by thermal imaging. Tissue response to hyperthermia, measured by immunohistochemical image analysis, reveals specific and localized heat-shock protein expression following treatment. Tumor growth inhibition is also observed. To evaluate the potential effects of MH on the immune landscape, flow cytometry is used to characterize immune cells from excised tumors and draining lymph nodes. Results show an influx of activated cytotoxic T cells, alongside an increase in proliferating regulatory T cells, following treatment. Complementary changes are found in draining lymph nodes. In conclusion, results indicate that biologically reactive MH is achievable in vivo and can generate localized changes consistent with an anti-tumor immune response.

Iron intake with the risk of breast cancer among Chinese women: a case-control study.

OBJECTIVE: The current study evaluated the associations between different forms and sources of Fe and breast cancer risk in Southern Chinese women. DESIGN: Case-control study. We collected data on the consumption of Fe from different forms and food sources by using a validated FFQ. Multivariable logistic regression and restricted cubic spline (RCS) analysis was used to reveal potential associations between Fe intake and breast cancer risk. SETTING: A case-control study of women at three major hospitals in Guangzhou, China. PARTICIPANTS: From June 2007 to March 2019, 1591 breast cancer cases and 1622 age-matched controls were recruited. RESULTS: In quartile analyses, Fe from plants and Fe from white meat intake were inversely associated with breast cancer risk, with OR of 0·65 (95 % CI 0·47, 0·89, Ptrend = 0·006) and 0·76 (95 % CI 0·61, 0·96, Ptrend = 0·014), respectively, comparing the highest with the lowest quartile. No associations were observed between total dietary Fe, heme or non-heme Fe, Fe from meat or red meat and breast cancer risk. RCS analysis demonstrated J-shaped associations between total dietary Fe, non-heme Fe and breast cancer, and reverse L-shaped associations between heme Fe, Fe from meat and Fe from red meat and breast cancer. CONCLUSION: Fe from plants and white meat were inversely associated with breast cancer risk. Significant non-linear J-shaped associations were found between total dietary Fe, non-heme Fe and breast cancer risk, and reverse L-shaped associations were found between heme Fe, Fe from meat or red meat and breast cancer risk.

Delay to surgery after neoadjuvant chemotherapy in head and neck squamous cell carcinoma affects oncologic outcomes.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is used in head and neck squamous cell carcinoma (HNSCC) for downstaging advanced disease and decreasing distant metastasis (DM). To the authors' knowledge, no study has specifically examined the impact of a delayed time to surgery (TTS) after NAC on oncologic outcomes. They thus aimed to identify a cutoff for TTS after NAC and its effect on survival indices. METHODS: This was a retrospective review of all patients with HNSCC receiving NAC followed by surgery with curative intent between March 2016 and March 2019 at the MD Anderson Cancer Center. Receiver operating characteristic analysis was used to identify a cutoff for TTS, and this cutoff was used to analyze the overall survival (OS), locoregional recurrence rate, DM-free rate, and disease-free survival (DFS). A multivariate Cox regression analysis was performed. RESULTS: One hundred one patients were analyzed with a median follow-up of 24.7 months. The 3-year OS and locoregional recurrence rates did not differ with a TTS ≥ 34 days. However, the 3-year DM-free rate was significantly worse (56% vs 90%; P = .001) in the group with a TTS ≥ 34 days, and the 3-year DFS was significantly lower (26% vs 64%; P = .006). In a multivariate analysis, a TTS ≥ 34 days (hazard ratio [HR], 4.92; 95% confidence interval [CI], 1.84-13.13) and extracapsular extension (HR, 3.01; 95% CI, 1.13-8.00) were significant independent predictors of a poorer DM-free rate. Weight loss > 10% (HR, 5.53; 95% CI, 1.02-30.24) was the only independent predictor for a TTS ≥ 34 days. CONCLUSIONS: Emphasis should be placed on early definitive locoregional treatment after NAC, particularly in patients who do not respond to NAC. There is a need to validate these findings and establish new benchmarks for the interval between NAC and surgery.

Personality and individual attitudes toward vaccination: a nationally representative survey in the United States.

BACKGROUND: Although past studies have identified factors associated with individual perceptions of vaccination, limited attention has been paid to the role of personality in individual attitudes toward vaccination. This study aimed to evaluate the effect of personality as measured by the Big Five personality traits on individual attitudes toward vaccination using a nationally representative survey in the United States. METHODS: A cross-sectional study was conducted with a sample of 3276 American citizens who were aged 18 and above and lived in 50 U.S. states and Washington D.C. from the American National Election Studies. The survey was collected through face-to-face and online interviews using structured questionnaires in 2016. The multistage stratified cluster sampling procedure was used for face-to-face interview, whereas the USPS DSF was used to select the sample for online interview. Multivariable ordinal logistic regression was used to assess how personality traits (extraversion, agreeableness, conscientiousness, emotional stability, and openness to experience) as main explanatory variables influence the outcome variables - individual attitudes toward health benefits of vaccination and support for school vaccination. RESULTS: More than two-thirds of respondents perceive health benefit of vaccination and support vaccination requirements for school entry, whereas about one-tenth of respondents have safety concerns about vaccination and oppose the vaccination requirements. After adjusting for ideology, insurance status, and demographic variables, the traits of agreeableness, conscientiousness and emotional stability remain significantly associated with attitude toward vaccination; conscientiousness is significantly associated with support for school vaccination. The odds of reporting health benefits of vaccination associated with one-point increase in agreeableness, conscientiousness and emotional stability are 1.05 (95% confidence intervals [CI] = 1.01-1.08), 1.05 (95% CI = 1.02-1.09) and 1.03 (95% CI = 1.00-1.06), respectively. For a one-point increase in conscientiousness, the odds of supporting school vaccination increase by 1.08 (95% CI = 1.05-1.12). CONCLUSIONS: People high in agreeableness, conscientiousness and emotional stability are more likely to regard vaccination as beneficial, whereas those high in conscientiousness are more likely to support school-based vaccine requirement. This study highlights the importance of personality in shaping individual attitudes toward vaccination. More research is needed to understand the role of personality in individual health attitudes and behavior.

Zinc oxide nanoparticles modulate the gene expression of ZnT1 and ZIP8 to manipulate zinc homeostasis and stress-induced cytotoxicity in human neuroblastoma SH-SY5Y cells.

Zinc ions (Zn2+) are important messenger molecules involved in various physiological functions. To maintain the homeostasis of cytosolic Zn2+ concentration ([Zn2+]c), Zrt/Irt-related proteins (ZIPs) and Zn2+ transporters (ZnTs) are the two families of proteins responsible for decreasing and increasing the [Zn2+]c, respectively, by fluxing Zn2+ across the membranes of the cell and intracellular compartments in opposite directions. Most studies focus on the cytotoxicity incurred by a high concentration of [Zn2+]c and less investigate the [Zn2+]c at physiological levels. Zinc oxide-nanoparticle (ZnO-NP) is blood brain barrier-permeable and elevates the [Zn2+]c to different levels according to the concentrations of ZnO-NP applied. In this study, we mildly elevated the [Zn2+]c by ZnO-NP at concentrations below 1 µg/ml, which had little cytotoxicity, in cultured human neuroblastoma SH-SY5Y cells and characterized the importance of Zn2+ transporters in 6-hydroxy dopamine (6-OHDA)-induced cell death. The results show that ZnO-NP at low concentrations elevated the [Zn2+]c transiently in 6 hr, then declined gradually to a basal level in 24 hr. Knocking down the expression levels of ZnT1 (located mostly at the plasma membrane) and ZIP8 (present in endosomes and lysosomes) increased and decreased the ZnO-NP-induced elevation of [Zn2+]c, respectively. ZnO-NP treatment reduced the basal levels of reactive oxygen species and Bax/Bcl-2 mRNA ratios; in addition, ZnO-NP decreased the 6-OHDA-induced ROS production, p53 expression, and cell death. These results show that ZnO-NP-induced mild elevation in [Zn2+]c activates beneficial effects in reducing the 6-OHDA-induced cytotoxic effects. Therefore, brain-delivery of ZnO-NP can be regarded as a potential therapy for neurodegenerative diseases.