Revisiting the complex time-varying effect of non-pharmaceutical interventions on COVID-19 transmission in the United States.

Introduction: Although the global COVID-19 emergency ended, the real-world effects of multiple non-pharmaceutical interventions (NPIs) and the relative contribution of individual NPIs over time were poorly understood, limiting the mitigation of future potential epidemics. Methods: Based on four large-scale datasets including epidemic parameters, virus variants, vaccines, and meteorological factors across 51 states in the United States from August 2020 to July 2022, we established a Bayesian hierarchical model with a spike-and-slab prior to assessing the time-varying effect of NPIs and vaccination on mitigating COVID-19 transmission and identifying important NPIs in the context of different variants pandemic. Results: We found that (i) the empirical reduction in reproduction number attributable to integrated NPIs was 52.0% (95%CI: 44.4, 58.5%) by August and September 2020, whereas the reduction continuously decreased due to the relaxation of NPIs in following months; (ii) international travel restrictions, stay-at-home requirements, and restrictions on gathering size were important NPIs with the relative contribution higher than 12.5%; (iii) vaccination alone could not mitigate transmission when the fully vaccination coverage was less than 60%, but it could effectively synergize with NPIs; (iv) even with fully vaccination coverage >60%, combined use of NPIs and vaccination failed to reduce the reproduction number below 1 in many states by February 2022 because of elimination of above NPIs, following with a resurgence of COVID-19 after March 2022. Conclusion: Our results suggest that NPIs and vaccination had a high synergy effect and eliminating NPIs should consider their relative effectiveness, vaccination coverage, and emerging variants.

Assessing the effectiveness of the expanded hepatitis A vaccination program in China: an interrupted time series design.

INTRODUCTION: China initialised the expanded hepatitis A vaccination programme (EHAP) in 2008. However, the effectiveness of the programme remains unclear. We aimed to comprehensively evaluate the effectiveness of EHAP in the country. METHODS: Based on the provincial data on the incidence of hepatitis A (HepA), the population and meteorological variables in China, we developed interrupted time series (ITS) models to estimate the effectiveness of EHAP with the autocorrelation, seasonality and the meteorological confounders being controlled. Results were also stratified by economic zones, age groups and provinces. RESULTS: We found a 0.9% reduction (RR=0.991, 95% CI: 0.990 to 0.991) in monthly HepA incidence after EHAP, which was 0.3% greater than the reduction rate before EHAP in China. Across the three economic regions, we found a 1.1% reduction in HepA incidence in both central and western regions after EHAP, which were 0.3% and 1.2% greater than the reduction rates before EHAP, respectively. We found a decreased reduction rate for the eastern region. In addition, we found generally increased reduction rate after EHAP for age groups of 0-4, 5-14 and 15-24 years. However, we found decreased reduction rate among the 25-64 and ≥65 years groups. We found a slight increased rate after EHAP in Shanxi Province but not elsewhere. CONCLUSION: Our finding provides comprehensive evidence on the effectiveness of EHAP in China, particularly in the central and western regions, and among the population aged 0-24 years old. This study has important implications for the adjustment of vaccination strategies for other regions and populations.

Physical activity and cancer risk: a dose-response analysis for the Global Burden of Disease Study 2019.

OBJECTIVE: Adopting a healthy lifestyle, including regular physical activity, is widely believed to decrease cancer risk. This study aimed to quantitatively establish the dose-response relationships between total physical activity and the risk of breast, colon, lung, gastric, and liver cancers. METHODS: A systematic review and dose-response analysis were conducted using PubMed and Embase from January 1, 1980 to March 20, 2023. Prospective cohort studies that examined the association between physical activity and the risks of any of the 5 outcomes were included. The search was confined to publications in the English language with a specific focus on human studies. Physical activity is standardized by using the data from US National Health and Nutrition Examination Surveys (NHANES) and the Global Burden of Disease 2019 database. RESULTS: A total of 98 studies, involving a combined population of 16,418,361 individuals, were included in the analysis. Among the included studies, 57 focused on breast cancer, 17 on lung cancer, 23 on colon cancer, 5 on gastric cancer, and 7 on liver cancer. Overall, elevated levels of physical activity exhibited an inverse correlation with the risk of cancer. The dose-response curve for lung cancer exhibited a non-linear pattern, with the greatest benefit risk reduction observed at 13,200 MET-minutes/week of physical activity, resulting in a 14.7% reduction in risk (relative risk 0.853, uncertainty interval 0.798 to 0.912) compared to the inactive population. In contrast, the dose-response curves for colon, gastric, breast, and liver cancers showed linear associations, indicating that heightened levels of total physical activity were consistently associated with reduced cancer risks. However, the increase in physical activity yielded a smaller risk reduction for colon and gastric cancers compared to breast and liver cancers. Compared to individuals with insufficient activity (total activity level < 600 MET-minutes/week), individuals with high levels of activity (≥ 8,000 MET-minutes/week) experienced a 10.3% (0.897, 0.860 to 0.934) risk reduction for breast cancer; 5.9% (0.941, 0.884 to 1.001) for lung cancer; 7.1% (0.929, 0.909 to 0.949) for colon cancer; 5.1% (0.949, 0.908 to 0.992) for gastric cancer; 17.1% (0.829, 0.760 to 0.903) for liver cancer. CONCLUSIONS: This study demonstrated a significant inverse relationship between total physical activity and the risk of breast, gastric, liver, colon, and lung cancers.

HVEM/HIF-1α promoted proliferation and inhibited apoptosis of ovarian cancer cells under hypoxic microenvironment conditions.

BACKGROUND: Our previous studies showed the expression of herpes virus entry mediator (HVEM) is high in ovarian cancer samples and correlated to the patient clinic pathological features. As we all know, the hypoxic environment is the main feature of tumor. In this work, we explored the role of HVEM in hypoxic ovarian cancer cells and its effects on HIF-1α, a transcription factor responding to hypoxia. METHODS: The expression of HVEM, HIF-1α and apoptosis-related genes was detected by qRT-PCR and western blot. The proliferation and apoptosis of the ovarian cancer cells were determined with the Cell Counting Kit-8 assay and AnnexinV-FITC/PI-stained flow cytometry assay, respectively. RESULTS: The expression of HVEM was positively correlated to that of HIF-1α. The expression of HVEM and HIF-1α under hypoxic conditions was higher than that under normoxic conditions, which suggested that the level of HVEM and HIF-1α correlates with prolonged periods of hypoxia in ovarian cancer. The overexpression of HVEM promoted cell proliferation and inhibited cell apoptosis under hypoxic condition. HVEM overexpression elevated the expression of HIF-1α and Bcl-2 (anti-apoptotic protein), and reduced the expression of Bax (pro-apoptotic protein). In addition, overexpression of HVEM activated the AKT/mTOR signaling. Moreover, knockdown of HVEM had the completely opposite effects. CONCLUSION: These data indicated that HVEM signaling might promote HIF-1α activity via AKT/mTOR signaling pathway and thus to regulate tumor growth in ovarian cancer under the hypoxic conditions. Furthermore, these findings indicate that this molecular mechanism could represent a therapeutic target for ovarian cancer.

Suppression of endothelial cell migration by tumor associated macrophage-derived exosomes is reversed by epithelial ovarian cancer exosomal lncRNA.

OBJECTIVE: To study the mechanism by which epithelial ovarian cancer (EOC)-derived exosomes restore the migration of endothelial cells that is suppressed by TAM-derived exosomes. METHODS: Exosomes were isolated from TAMs in the ascites of patients with EOC. The effect of exosomes on the expression of endothelial cell miRNA was monitored by PCR. The miRNA mimics were transfected to explore their effects. Microarray data and literature searches were used to predict target genes and the impact of target gene pathways, and small interfering RNA was used to target these genes. We used migration assays to determine whether ovarian cancer cell-derived exosomes participate in the regulation of TAMs and endothelial cells. We used microarray data to identify the target lncRNA, and we constructed target lncRNA expression plasmids to validate targets by Western blotting. RESULTS: We separated TAMs from the ascites of patients with EOC and isolated exosomes from TAM supernatants. After co-culture with HUVECs, these exosomes were efficiently incorporated into HUVECs. The migration of HUVECs was suppressed significantly in the exosome group compared with blank controls (P < 0.05).The miRNA mimic transfection and target gene prediction found that TAM-derived exosomes targeted the miR-146b-5p/TRAF6/NF-κB/MMP2 pathway to suppress endothelial cell migration; this result was supported by PCR and Western blotting analyses. The expression of exosomal miR-146b-5p isolated from serum in the EOC group was significantly increased compared to healthy individuals. Finally, TAM-derived exosomes and EOC SKOV3-derived exosomes in combination stimulated HUVEC cells and overcame the inhibition of endothelial cell migration caused by TAM-derived exosomes. Two lncRNAs that were carried by SKOV3-derived exosomes were identified as NF-κB pathway-associated genes by Western blotting. CONCLUSION: TAM-derived exosomes can inhibit the migration of endothelial cells by targeting the miR-146b-5p/TRAF6/NF-kB/MMP2 pathway. However, EOC-derived exosomes can transfer lncRNAs to remotely reverse this effect of TAMs on endothelial cells.

Computation of radiation pressure force exerted on arbitrary shaped homogeneous particles by high-order Bessel vortex beams using MLFMA.

Due to special characteristics of nondiffraction and self reconstruction, the Bessel beams have attracted wide attention in optical trapping and appear to be a dramatic alternative to Gaussian beams. We present in this paper an efficient approach based on the surface integral equations (SIE) to compute the radiation pressure force (RPF) exerted on arbitrary shaped homogeneous particles by high-order Bessel vortex beam (HOBVB). The incident beam is described by vector expressions perfectly satisfy Maxwell's equations. The problem is formulated with the combined tangential formulation (CTF) and solved iteratively with the aid of the multilevel fast multipole algorithm (MLFMA). Then RPF is computed by vector flux of the Maxwell's stress tensor over a spherical surface tightly enclosing the particle and analytical expression for electromagnetic fields of incident beam in near region are used. The numerical predictions are compared with the results of the rigorous method for spherical particle to validate the accuracy of the approach. Some numerical results on relative large particles of complex shape, such as biconcave cell-like particles with different geometry parameters are given, showing powerful capability of our approach. These results are expected to provide useful insights into the RPF exerted on complex shaped particles by HOBVB.

Interaction between Treg cells and tumor-associated macrophages in the tumor microenvironment of epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy. Inflammatory cells in the EOC microenvironment play a key role in tumor progression. In the present study, we investigated the mechanism of the accumulation of regulatory T cells (Tregs) induced by interleukin-10 (IL-10) derived from tumor-associated macrophages (TAMs) in the EOC microenvironment. The frequency of Tregs and TAMs was detected by immunofluorescence in 40 EOC tissues and 20 benign ovarian tumors, as well as the expression of IL-10 which was assessed by immunohistochemistry. It was found that the frequency of Treg cells and TAMs was significantly higher in the EOC than those in the benign ovarian tumors. The expression of IL-10 was also found to be higher in the EOC than that in the benign tumors. EOC patients with a high frequency of Tregs exhibited a significantly shorter overall survival time compared to those with a low frequency of Tregs. In addition, the expression of IL-10 in ascites and blood serum and the IL-10 released in the co-cultured system supernatants were detected by ELISA. Following CD4+ T-cell co-culturing with macrophages and IL-10, it was observed by flow cytometric analysis that the frequency of Treg cells was increased in the presence of IL-10. It was also established that IL-10 released in the co-cultured supernatants was increased. We also detected the mechanism of Treg cells induced by IL-10 in vivo. The SKOV3 cell tumor volume and weight were much higher in the presence of IL-10 in a mouse subcutaneous model. These data suggest that IL-10 secreted by TAMs increase the frequency of Treg cells through the activation of Foxp3 during T-cell differentiation and promotes tumor progression.

Prediction of endometrial carcinogenesis probability while diagnosed as atypical endometrial hyperplasia: a new risk model based on age, CA199 and CA125 assay.

OBJECTIVE: To establish a risk model for predicting the probability of endometrial carcinogenesis while diagnosed as AEH preoperatively. STUDY DESIGN: 149 patients with AEH diagnosed by D&C specimens or hysteroscopy undergoing total hysterectomy were enrolled in this retrospective study. Patients were divided into two groups: 51 cases in AEH to AEH group and 98 cases in AEH to EC group. The clinical pathological characteristics were compared between the two groups. With the use of ROC curves, cutoff values of age, CA199, CA125 and uterine height were determined. The relationships of these evaluators with endometrial carcinogenesis were investigated by multivariate analysis with a logistic regression model. RESULTS: 65.8% (98/149) of preoperative AEH patients become EC after confirmed by paraffin hysterectomy specimens. The cutoff values were 51.5 years of age, 14.06U/ml of CA199, 14.30U/ml of CA125 and 45mm of uterine height, respectively. Logistic regression analysis demonstrated age (OR=0.58, 95% confidence interval [95%CI]: 0.08-3.94), CA199 (OR=7.27, 95%CI: 1.43-36.92), CA125 (OR=13.97, 95%CI: 2.49-78.37), uterine height (OR=0.49, 95%CI: 0.08-3.08) and abnormal uterine bleeding (OR=4.27, 95%CI: 0.53-34.52) were associated with endometrial carcinogenesis. However, only CA199 (p=0.017) and CA125 (p=0.003) revealed significant differences. Therefore, when entered into the risk model, CA199≥14.06U/ml and CA125≥14.30U/ml were considered as cogent predictors of endometrial carcinogenesis. CONCLUSIONS: This risk model may well predict the probability of endometrial carcinogenesis when preoperatively diagnosed as AEH.

Computation of stress on the surface of a soft homogeneous arbitrarily shaped particle.

Prediction of the stress on the surface of an arbitrarily shaped particle of soft material is essential in the study of elastic properties of the particles with optical force. It is also necessary in the manipulation and sorting of small particles with optical tweezers, since a regular-shaped particle, such as a sphere, may be deformed under the nonuniform optical stress on its surface. The stress profile on a spherical or small spheroidal soft particle trapped by shaped beams has been studied, however little work on computing the surface stress of an irregular-shaped particle has been reported. We apply in this paper the surface integral equation with multilevel fast multipole algorithm to compute the surface stress on soft homogeneous arbitrarily shaped particles. The comparison of the computed stress profile with that predicted by the generalized Lorenz-Mie theory for a water droplet of diameter equal to 51 wavelengths in a focused Gaussian beam show that the precision of our method is very good. Then stress profiles on spheroids with different aspect ratios are computed. The particles are illuminated by a Gaussian beam of different waist radius at different incidences. Physical analysis on the mechanism of optical stress is given with help of our recently developed vectorial complex ray model. It is found that the maximum of the stress profile on the surface of prolate spheroids is not only determined by the reflected and refracted rays (orders p=0,1) but also the rays undergoing one or two internal reflections where they focus. Computational study of stress on surface of a biconcave cell-like particle, which is a typical application in life science, is also undertaken.