A multidisciplinary effort to increase COVID-19 vaccination among the older adults.

Background: COVID-19 vaccination significantly reduces the risk of infection and its associated morbidity and mortality. However, poor uptake of the COVID-19 vaccination was reported among the high-risk group of older people amidst emerging variants of concern. This community case study reports an outreach program in Singapore, COVE (COVID-19 Vaccination for the Elderly) initiated by healthcare workers in a cluster of primary care clinics. They assessed the vaccine hesitancy among these older persons, addressed their concerns and facilitated their vaccination appointment during a brief phone conversation. Method: Twenty one thousand six hundred and sixty three unvaccinated adults aged ≥60 years were contacted by healthcare worker volunteers over two phases from June to October 2021. In phase I, they contacted adults aged above 70 years over 2 weeks. Adults who were uncontactable in phase I and those aged 60-69 years were sent SMS in phase II. Data were analyzed via descriptive data analysis. Results: After phase 1, 65.5% (n = 5,646/8,617) of older adults had received at least one dose of the COVID-19 vaccine. The respondents expressed intention to vaccinate (39%, n = 3,390), requested to seek further information (25%, n = 2,138), reported access barrier (8%, n = 715), or were concerned of the vaccine adverse effects (3%, n = 288). Vaccination was refused by 24% (n = 2,086) of the respondents. Eventually 60.4% (n = 13,082/21,663) of them were vaccinated 3 months after COVE implementation. Conclusion: The COVE program increased the COVID-19 vaccination uptake of older adults from 84.6 to 96.3%. A person-centric proactive approach by healthcare workers addressed vaccine hesitancy and optimized vaccination. The outreach scheduling of vaccination appointments is key in promoting vaccination uptake among older adults.

The Implementation and Impact of a Revised National Childhood Immunization Schedule in an Urban Asian Community.

Changes to the national childhood immunization schedule (NCIS) can have a potential impact on vaccine uptake in the community. The NCIS in Singapore has undergone several revisions over the years, with the most recent modification on 1 November 2020. The new NCIS includes, as routine, the influenza and the varicella vaccine, as well as two combination vaccines, the measles, mumps, rubella and varicella vaccine (MMRV), and the hexavalent diphtheria, acellular pertussis, tetanus, haemophilus influenza b, injectable polio, and hepatitis B vaccine (6-in-1). This retrospective database study aims to assess the effect of the new NCIS on (a) the vaccination uptake of children at 6 and 12 months and (b) the cost difference to the healthcare system and to parents. One-year vaccination data from two cohorts of children immunized according to the old (n = 10,916) and new NCIS (n = 10,299) were extracted, respectively, from their electronic medical records. The vaccine uptake at 6 and 12 months increased by 10.8 and 2.1%, respectively, with the new NCIS as compared to the old NCIS. The mean number of required visits to the primary care clinic for each child was reduced from six to four. There is an estimated 6.41% cost reduction with the new NCIS.

IGFBP7 overexpression promotes acquired resistance to AZD9291 in non-small cell lung cancer.

AZD9291 (osimertinib) is the third-generation EGFR-TKI treat for EGFR mutated NSCLC patients. Despite its encouraging efficacy in clinical, acquired resistance is still inevitable. The mechanism of drug resistance needs to be further explored. In a previous study, we established an AZD9291-resistant cell strain named HCC827/AZDR. We found that insulin-like growth factor binding protein 7 (IGFBP7) expression was markedly increased in HCC827/AZDR cells and AZD9291-resistant patients by RNA sequencing and immunohistochemical analysis, respectively. Reduced IGFBP7 in HCC827/AZDR cells by si-RNA interference recovered the sensitivity to AZD9291 partially and increased AZD9291-induced cell apoptosis. Enhancing IGFBP7 expression in EGFR-mutated non-small cell lung cancer (NSCLC) cells using lentiviruses infection reduced their sensitivity to AZD9291. This study is the first to discover that high IGFBP7 expression could occur following treatment with AZD9291. This might be one of the mechanisms underlying AZD9291 resistance and a potential therapeutic target following AZD9291 resistance.

[CD45RO⁺ Memory T Lymphocytes As A Candidate Marker for Non-small Cell Lung Cancer].

BACKGROUND: Lung cancer is the most common malignancy world-wide. There are a variety of immune infiltrating cells in tumor microenvironment, which is an important component of tumor immunity and has clinical significance for the prognosis of patients. CD45RO is a surface marker of memory T cells. The expression of CD45RO⁺ tumor infiltrating lymphocytes (TILs) is associated with the prognosis of many tumors. The purpose of this study was to evaluate the relationship between the density of CD45RO⁺ TILs in tumor and stromal area and the clinical characteristics of patients with non-small cell lung cancer (NSCLC) and its impact on the prognosis of patients. We aimed to explore the clinical value of CD45RO⁺ TILs and programmed cell death ligand 1 (PD-L1) as prognostic markers. METHODS: Multiple fluorescent immunohistochemical staining was used to stain the tissue microarray chips of 167 patients with NSCLC, marking CD45RO, cytokeratin (CK) and PD-L1. Using artificial intelligence image recognition technology and tumor cell-specific CK staining, divide the tumor and stromal area in the tissue, evaluate the density of CD45RO⁺ TILs in the tumor and stromal area, and the expression level of PD-L1 in tumor cells. The non-parametric test was used to analyze the relationship between CD45RO⁺ TILs and the clinical characteristics of patients, and the Kaplan-Meier method and Cox risk ratio model were used to analyze the relationship between CD45RO⁺ TILs independently or in combination with PD-L1 and tumor prognosis. RESULTS: The density of CD45RO⁺ TILs was significantly associated with patient age, smoking, tumor stage, and pathological type. Single-factor survival analysis showed that NSCLC (P=0.007) stromal region and lung adenocarcinoma (LUAD) (P<0.001) with CD45RO⁺ TILs high density had better OS. Multivariate survival analysis showed that the high density of CD45RO⁺ TILs in the stromal region of NSCLC (HR=0.559, 95%CI: 0.377-0.829, P=0.004) and lung adenocarcinoma (HR=0.352, 95%CI: 0.193-0.641, P=0.001) were independent prognostic factors for overall survival time (OS). Combined with PD-L1 score of tumor cells in tumor tissues and infiltration score of CD45RO⁺ TILs in all tumor tissues, the patients were divided into 4 groups: patients with PD-L1⁺/CD45RO⁺ had the longest disease-free survival (DFS) time, and patients with PD-L1⁺/CD45RO- had the shortest DFS time. Multivariate Cox regression analysis showed that PD-L1⁺/CD45RO- was an independent prognostic factor for DFS and had a higher risk of poor prognosis compared to the other three groups (HR=2.221, 95%CI: 1.258-3.919, P=0.006). CONCLUSIONS: In tumor tissues, the density of CD45RO⁺ TILs, as well as the combination of CD45RO⁺ TILs and PD-L1 in tumor areas, significantly correlated with clinicopathological features and prognosis of NSCLC, which can be used as a new prognosis marker.

An Urban Scaling Estimation Method in a Heterogeneity Variance Perspective.

Urban scaling laws describe powerful universalities of the scaling relationships between urban attributes and the city size across different countries and times. There are still challenges in precise statistical estimation of the scaling exponent; the properties of variance require further study. In this paper, a statistical regression method based on the maximum likelihood estimation considering the lower bound constraints and the heterogeneous variance of error structure, termed as CHVR, is proposed for urban scaling estimation. In the CHVR method, the heterogeneous properties of variance are explored and modeled in the form of a power-of-the-mean variance model. The maximum likelihood fitting method is supplemented to satisfy the lower bound constraints in empirical data. The CHVR method has been applied to estimating the scaling exponents of six urban attributes covering three scaling regimes in China and compared with two traditional methods. Method evaluations based on three different criteria validate that compared with both classical methods, the CHVR method is more effective and robust. Moreover, a statistical test and long-term variations of the parameter in the variance function demonstrate that the proposed heterogeneous variance function can not only describe the heterogeneity in empirical data adequately but also provide more meaningful urban information. Therefore, the CHVR method shows great potential to provide a valuable tool for effective urban scaling studies across the world and be applied to scaling law estimation in other complex systems in the future.