Search

Abstract Background We investigated the synergistic effect of stress and habitual salt preference (SP) on blood pressure (BP) in the hospitalized Omicron-infected patients. Methods From 15,185 hospitalized Omicron-infected patients who reported having high BP or hypertension, we recruited 662 patients. All patients completed an electronic questionnaire on diet and stress, and were required to complete morning BP monitoring at least three times. Results The hypertensive group (n = 309) had higher habitual SP (P = 0.015) and COVID-19 related stress (P

Dengue fever, a mosquito-borne disease caused by the dengue virus, imposes a substantial disease burden on the world. Wolbachia not only manipulates the reproductive processes of mosquitoes through maternal inheritance and cytoplasmic incompatibility (CI) but also restrain the replication of dengue viruses within mosquitoes, becoming a novel approach for biologically combating dengue fever. A combined use of Wolbachia and insecticides may help to prevent pesky mosquito bites and dengue transmission. A model with impulsive spraying insecticide is introduced to examine the spread of Wolbachia in wild mosquitoes. We prove the stability and permanence results of periodic solutions in the system. Partial rank correlation coefficients (PRCCs) can determine the importance of the contribution of input parameters on the value of the outcome variable. PRCCs are used to analyze the influence of input parameters on the threshold condition of the population replacement strategy. We then explore the impacts of mosquito-killing rates and pulse periods on both population eradication and replacement strategies. To further investigate the effects of memory intensity on the two control strategies, we developed a Caputo fractional-order impulsive mosquito population model with integrated control measures. Simulation results show that for the low fecundity scenario of individuals, as memory intensity increases, the mosquito eradication strategy will occur at a slower speed, potentially even leading to the mosquito replacement strategy with low female numbers. For the high fecundity scenario of individuals, with increasing memory intensity, the mosquito replacement strategy will be achieved more quickly, with lower mosquito population amplitudes and overall numbers. It indicates that although memory factors are not conducive to implementing a mosquito eradication strategy, achieving the replacement strategy with a lower mosquito amount is helpful. This work will be advantageous for developing efficient integrated control strategies to curb dengue transmission.

ObjectivesThe relationship between statin treatment and fracture risk is still controversial, especially in in patients with cardiovascular diseases (CVDs). We aim to determine whether statin therapy affects the occurrence of fractures in the general US population and in patients with CVDs.MethodsEpidemiological data of this cross-sectional study were extracted from the National Health and Nutrition Examination Survey (NHANES, 2001-2020, n = 9,893). Statins records and fracture information were obtained from the questionnaires. Weighted logistic regressions were performed to explore the associations between statin and the risk of fracture.ResultsStatin use was found to be associated with reduced risk of fracture mainly in male individuals aged over 50 years old and taking medications for less than 3 years, after adjusted for confounders including supplements of calcium and vitamin D. The protective effects were only found in subjects taking atorvastatin and rosuvastatin. We found null mediation role of LDL-C and 25(OH)D in such effects. Statin was found to reduce fracture risk in patients with cardiovascular diseases (CVDs, OR: 0.4366, 95%CI: 0.2664 to 0.7154, P = 0.0014), and in patients without diabetes (OR: 0.3632, 95%CI: 0.1712 to 0.7704, P = 0.0091).ConclusionsStatin showed advantages in reducing risk of fracture in male individuals aged over 50 years old and taking medications for less than 3 years. More research is needed to determine the impact of gender variations, medication duration, and diabetes.

Abstract Background Countries that aimed for eliminating the cases of COVID-19 with test-trace-isolate policy are found to have lower infections, deaths, and better economic performance, compared with those that opted for other mitigation strategies. However, the continuous evolution of new strains has raised the question of whether COVID-19 eradication is still possible given the limited public health response capacity and fatigue of the epidemic. We aim to investigate the mechanism of the Zero-COVID policy on outbreak containment, and to explore the possibility of eradication of Omicron transmission using the citywide test-trace-isolate (CTTI) strategy. Methods We develop a compartmental model incorporating the CTTI Zero-COVID policy to understand how it contributes to the SARS-CoV-2 elimination. We employ our model to mimic the Delta outbreak in Fujian Province, China, from September 10 to October 9, 2021, and the Omicron outbreak in Jilin Province, China for the period from March 1 to April 1, 2022. Projections and sensitivity analyses were conducted using dynamical system and Latin Hypercube Sampling/ Partial Rank Correlation Coefficient (PRCC). Results Calibration results of the model estimate the Fujian Delta outbreak can end in 30 (95% confidence interval CI: 28–33) days, after 10 (95% CI: 9–11) rounds of citywide testing. The emerging Jilin Omicron outbreak may achieve zero COVID cases in 50 (95% CI: 41–57) days if supported with sufficient public health resources and population compliance, which shows the effectiveness of the CTTI Zero-COVID policy. Conclusions The CTTI policy shows the capacity for the eradication of the Delta outbreaks and also the Omicron outbreaks. Nonetheless, the implementation of radical CTTI is challenging, which requires routine monitoring for early detection, adequate testing capacity, efficient contact tracing, and high isolation compliance, which constrain its benefits in regions with limited resources. Moreover, these challenges become even more acute in the face of more contagious variants with a high proportion of asymptomatic cases. Hence, in regions where CTTI is not possible, personal protection, public health control measures, and vaccination are indispensable for mitigating and exiting the COVID-19 pandemic. Graphical Abstract

Hepatitis B is a disease that damages the liver, and its control has become a public health problem that needs to be solved urgently. In this paper, we investigate analytically and numerically the dynamics of a new stochastic HBV infection model with antiviral therapies and immune response represented by CTL cells. Through using the theory of stochastic differential equations, constructing appropriate Lyapunov functions and applying Itô's formula, we prove that the disease-free equilibrium of the stochastic HBV model is stochastically asymptotically stable in the large, which reveals that the HBV infection will be eradicated with probability one. Moreover, the asymptotic behavior of globally positive solution of the stochastic model near the endemic equilibrium of the corresponding deterministic HBV model is studied. By using the Milstein's method, we provide the numerical simulations to support the analysis results, which shows that sufficiently small noise will not change the dynamic behavior, while large noise can induce the disappearance of the infection. In addition, the effect of inhibiting virus production is more significant than that of blocking new infection to some extent, and the combination of two treatment methods may be the better way to reduce HBV infection and the concentration of free virus.

Although some methods for estimating the instantaneous reproductive number during epidemics have been developed, the existing frameworks usually require information on the distribution of the serial interval and/or additional contact tracing data. However, in the case of outbreaks of emerging infectious diseases with an unknown natural history or undetermined characteristics, the serial interval and/or contact tracing data are often not available, resulting in inaccurate estimates for this quantity. In the present study, a new framework was specifically designed for joint estimates of the instantaneous reproductive number and serial interval. Concretely, a likelihood function for the two quantities was first introduced. Then, the instantaneous reproductive number and the serial interval were modeled parametrically as a function of time using the interpolation method and a known traditional distribution, respectively. Using the Bayesian information criterion and the Markov Chain Monte Carlo method, we ultimately obtained their estimates and distribution. The simulation study revealed that our estimates of the two quantities were consistent with the ground truth. Seven data sets of historical epidemics were considered and further verified the robust performance of our method. Therefore, to some extent, even if we know only the daily incidence, our method can accurately estimate the instantaneous reproductive number and serial interval to provide crucial information for policymakers to design appropriate prevention and control interventions during epidemics.

Abstract Background and Aims Interleukin‐2 (IL‐2) can be used as an adjuvant therapy when pegylated interferon alpha (Peg‐IFN‐α) does not effectively promote hepatitis B surface antigen (HBsAg) loss, but the relevant timing, kinetic patterns, and prognostic associations of this intervention are unclear. Methods A total of 115 patients with chronic hepatitis B (CHB) treated at our institution between October 2018 and March 2021 were included in this retrospective analysis. They were divided into two kinetic patterns by using K‐medoids cluster analysis. Profile and prognostic associations were statistically analyzed between the two patterns. Results After baseline standardization, before the intervention, the relative HBsAg level showed a continuously increasing trend, but after the intervention, it showed a continuously decreasing trend. Based on the relative change in the HBsAg level, two kinetic patterns, namely, a fluctuation platform pattern and a stepwise growth pattern, were identified by using K‐medoids cluster analysis for all 115 patients before IL‐2 intervention. Profile analysis showed that there were statistically significant differences between the two patterns before IL‐2 intervention (p

Abstract Purpose Previous clinical studies have suggested an effect of gender on outcome after out-of-hospital cardiac arrest, but the results are conflicting and there is no uniform agreement regarding gender differences in survival and prognosis. The present study was aimed to investigate the interaction between gender and post resuscitation interventions on neurological outcome in an asphyxial rat model of cardiac arrest. Methods Asphyxia was induced by blocking the endotracheal tube in 120 adult Sprague–Dawley rats (60 males and 60 females) at the same age. Cardiopulmonary resuscitation (CPR) was started after 5 min of untreated cardiac arrest. Animals were randomized into one of the three post resuscitation care intervention groups (n = 40, 20 males) immediately after resuscitation: (1) normothermic control (NC): ventilated with 2% N2/98% O2 for 1 h under normothermia; (2) targeted temperature management (TTM): ventilated with 2% N2/98% O2 for 1 h under hypothermia; (3) hydrogen inhalation (HI): ventilated with 2% H2/98% O2 for 1 h under normothermia. Physiological variables were recorded during the 5 h post resuscitation monitoring period. Neurological deficit score (NDS) and accumulative survival were used to assess 96 h outcomes. Mutual independence analysis and Mantel–Haenszel stratified analysis were used to explore the associations among gender, intervention and survival. Results The body weights of female rats were significantly lighter than males, but CPR characteristics did not differ between genders. Compared with male rats, females had significantly lower mean arterial pressure, longer onset time of the electroencephalogram (EEG) burst and time to normal EEG trace (TTNT) in the NC group; relatively longer TTNT in the TTM group; and substantially longer TTNT, lower NDSs, and higher survival in the HI group. Mutual independence analysis revealed that both gender and intervention were associated with neurological outcome. Mantel–Haenszel stratified analysis demonstrated that female rats had significantly higher survival rate than males when adjusted for the confounder intervention. Conclusion In this rat model cardiac arrest and CPR, gender did not affect resuscitation but associated with neurological outcome. The superiority of female rats in neurological recovery was affected by post resuscitation interventions and female rats were more likely to benefit from hydrogen therapy.

A viral infection model with self-proliferation of cytotoxic T lymphocytes (CTLs) is proposed and its global dynamics is obtained. When the per capita self-proliferation rate of CTLs is sufficient large, an infection-free but immunity-activated equilibrium always exists and is globally asymptotically stable if the basic reproduction number of virus is less than a threshold value, which means that the immune effect still exists though virus be eliminated. Qualitative numerical simulations further indicate that the increase of per capita self-proliferation rate may lead to more severe infection outcome, which may provide insight into the failure of immune therapy.

In this paper, considering the proven role of exosomes and the inevitable randomization within-host, we establish a hepatitis B virus (HBV) model with cell-to-cell transmission and CTL immune response from a deterministic framework to a stochastic differential equation (SDE). By introducing the reproduction number $R_0$, we prove that $R_0$ can be used to govern the stochastic dynamics of the SDE HBV model. Under certain assumptions, if $R_{0}\leq1$, the solution of the SDE model always fluctuates around the infection-free equilibrium of the deterministic model, which indicates that the HBV will eventually disappear almost surely; if $R_{0}>1$, under extra conditions, the solution of the SDE model fluctuates around endemic equilibrium of the corresponding deterministic model, which leads to the stochastic persistence of the HBV with probability one. One of the most interesting findings is that the fluctuation amplitude is positively related to the intensity of the white noise, which can provide us some useful control strategies to regulate HBV infection dynamics.

In theory, pure competition often leads to competitive exclusion of species. However, what we often see in nature is a large number of distinct predator or consumer species coexist in a community consisting a smaller number of prey or plant species. In an effort of dissecting how indirect competition and selective predation may have contributed to the coexistence of species in an insect community, according to the replicated cage experiments (two aphid species and a specialist parasitoid that attacks only one of the aphids) and proposed mathematical models, van Veen et. al. [5] conclude that the coexistence of the three species is due to a combination of density-mediated and trait-mediated indirect interactions. In this paper, we formulate an alternative model that observes the conventional law of mass conservation and provides a better fitting to their experimental data sets. Moreover, we present an initial attempt in studying the stabilities of the nonnegative steady states of this model.

A new mathematical model was proposed to study the effect of self-proliferation and delayed activation of immune cells in the process of virus infection. The global stability of the boundary equilibria was obtained by constructing appropriate Lyapunov functional. For positive equilibrium, the conditions of stability and Hopf bifurcation were obtained by taking the delay as the bifurcation parameter. Furthermore, the direction and stability of the Hopf bifurcation are derived by using the theory of normal form and center manifold. These results indicate that self-proliferation intensity can significantly affect the kinetics of viral infection, and the delayed activation of immune cells can induce periodic oscillation scenario. Along with the increase of delay time, numerical simulations give the corresponding bifurcation diagrams under different self-proliferation rates, and verify that there exists stability switch phenomenon under some conditions.

The outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still severe. In order to optimize the epidemic response strategy, it is urgent to evaluate the implemented prevention and control interventions (PCIs). Based on the reported data of Chongqing and Guizhou Provinces, the phased dynamic models of COVID-19 were constructed, the average intensity of the existing PCIs (from January 25 to March 2) was estimated in these two provinces. The results indicate that both provinces have carried out better control of the infected, but there are still differences in the intensity of control for people who need close observation. Especially in Chongqing, the estimated strength is significantly smaller than that in Guizhou. Furthermore, qualitative evaluations on the epidemic of COVID-19 under different PCIs scenarios suggest that containment strategy is still necessary to ensure the safety of resumption of work and school, and quarantining the city of Wuhan is an important and effective containment strategy to reduce the epidemic in other provinces.

Varicella (chickenpox) is highly contagious among children and frequently breaks out in schools. In this study, we developed a dynamic compartment model to explore the optimal schedule for varicella vaccination in Jiangsu Province, China. A susceptible-infected-recovered (SIR) model was proposed to simulate the transmission of varicella in different age groups. The basic reproduction number was computed by the kinetic model, and the impact of three prevention factors was assessed through the global sensitivity analysis. Finally, the effect of various vaccination scenarios was qualitatively evaluated by numerical simulation. The estimated basic reproduction number was 1.831 ± 0.078, and the greatest contributor was the 5–10 year-old group (0.747 ± 0.042, 40.80%). Sensitivity analysis indicated that there was a strong negative correlation between the second dose vaccination coverage rate and basic reproduction number. In addition, we qualitatively found that the incidence would significantly decrease as the second dose vaccine coverage expands. The results suggest that two-dose varicella vaccination should be mandatory, and the optimal age of second dose vaccination is the 5–10 year-old group. Optimal vaccination time, wide vaccine coverage along with other measures, could enhance the effectiveness of prevention and control of varicella in China.

Background: Several outbreaks of severe hand-foot-mouth disease (HFMD) in East Asia and Southwest Asia in recent years have had a serious impact on the countries. However, the factors that contribute to annual multiple-peak pattern of HFMD outbreaks, and how and when do these factors play the decisive role in the HFMD transmission is still unclear. Methods: Based on the surveillance data of HFMD between 1 January 2010 to 31 December 2015 in Wenzhou, China, the daily modelfree basic reproduction number and its annual average were first estimated by incorporating incubation and infection information, then the annual model-based basic reproduction number was computed by the proposed kinetic model, and finally the potential impact factors of multiple-peak pattern are assessed through the global and time-varying sensitivity analyses. Results: All annual model-based and model-free basic reproduction numbers were significantly higher than one. The school opening both in the spring and fall semester, meteorological e ect in the spring semester, and the interactions among them were strongly correlated with the annual model-based basic reproduction number, which were the main underlying factors on the annual multiple-peak pattern of HFMD outbreaks. Conclusions: School opening was primarily responsible for peaks of HFMD outbreaks and meteorological factors in the spring semester should also be highly concerned. The optimum timing for social distance implementation is at the beginning of every school semester and health education focusing on personal hygiene and good sanitation should be highlighted in the spring semester.

Immune thrombocytopenia (ITP) is an autoimmune disease which arises due to self-destruction of circulating platelets. Failure to respond or maintain a response to first-line treatment can lead to refractory/relapsed (R/R) ITP. The mechanism remains complicated and lacks a standard clinical treatment. Sirolimus (SRL) is a mammalian target of rapamycin (mTOR) inhibitor that has been demonstrated to inhibit lymphocyte activity, indicating potential for SRL in treatment of ITP. Activation of the mTOR pathway in autoimmune diseases suggests that SRL might be a useful agent for treating ITP. Accordingly, we initiated an open-label, prospective clinical trial using SRL for patients with R/R ITP (ChiCTR-ONC-17012126). The trial enrolled 86 patients, each dosed with 2–4 mg/day of SRL. By the third month, 40% of patients (34 of 86) achieved complete remission (CR) and 45% of patients (39 of 86) achieved partial remission (PR), whereby establishing an overall response rate (ORR) of 85%. By 6 months of treatment, 41% of patients (32 of 78) achieved CR and 29% of patients (23 of 78) achieved PR, establishing an ORR of 70% without serious side effects. After 12 months follow-up, the ORR remained at 65%. We also found that SRL treatment exhibited higher efficacy in achieving CR in ITP patients who were younger than 40 years old or steroid dependent by univariate analysis. Importantly, in patients who responded, SRL treatment was associated with a reduction in the percentage of Th2, Th17 cells, and increase in the percentage of M-MDSCs and Tregs, indicating that SRL may reestablish peripheral tolerance. Taken together, Sirolimus demonstrated efficacy as a second-line agent for R/R ITP.

In this study, a sandwich piezoelectric nano-energy harvester model under compressive axial loading with a core layer fabricated of functionally graded (FG) porous material is presented based on the nonlocal strain gradient theory (NSGT). The von Karman type geometric nonlinearity and the axial loading were considered. The electromechanical governing equations were obtained using Hamilton’s principle. The nonlinear vibration frequencies, root mean square (RMS) voltage output and static buckling were obtained using the Galerkin method. The effects of different types of porous distribution, porosity coefficients, length scale parameters, nonlocal parameters, flexoelectricity, excitation frequencies, lumped mass and axial loads on the natural frequency and voltage output of nanobeams were investigated. Results show that the porous distributions, porosity coefficient of porous materials, the excitation frequencies and the axial load have a large effect on the natural frequency and voltage output of the sandwiched piezoelectric nanobeams. When the NSGT is considered, the critical buckling load depends on the values of the nonlocal parameters and strain gradient constants. In addition, the electromechanical conversion efficiency of the post-buckling process is significantly higher than that of the pre-buckling process. The flexoelectric effect can significantly increase the RMS voltage output of the energy harvester.

This paper investigates the dynamic behavior of a viral infection model with general contact rate between susceptible host cells and free virus particles. If the basic reproduction number of the virus is less than unity, by LaSalle’s invariance principle, the disease-free equilibrium is globally asymptotically stable. If the basic reproduction number of the virus is greater than unity, then the virus persists in the host and the endemic equilibrium is locally asymptotically stable.

To quantitatively study the effect of delay on selection dynamics in long-term sphere culture of cancer stem cells (CSCs), a selection dynamic model with time delay is proposed. Theoretical results show that the ubiquitous time delay in cell proliferation may be one of the important factors to induce fluctuation, and numerical simulations indicate that the proposed selection dynamical model with time delay can provide a better fitting effect for the experiment of a long-term sphere culture of CSCs. Thus, it is valuable to consider the delay effect in the future study on the dynamics of nongenetic heterogeneity of clonal cell populations.

A novel dynamic model covering five types of cells and three connected compartments, peripheral blood (PB), lymph nodes (LNs), and the central nervous system (CNS), is here proposed. It is based on assessment of the biological principles underlying the interactions between the human immunodeficiency virus type I (HIV-1) and the human immune system. The simulated results of this model matched the three well-documented phases of HIV-1 infection very closely and successfully described the three stages of LN destruction that occur during HIV-1 infection. The model also showed that LNs are the major location of viral replication, creating a pool of latently infected T4 cells during the latency period. A detailed discussion of the role of monocytes/macrophages is made, and the results indicated that infected monocytes/macrophages could determine the progression of HIV-1 infection. The effects of typical highly active antiretroviral therapy (HAART) drugs on HIV-1 infection were analyzed and the results showed that efficiency of each drug but not the time of the treatment start contributed to the change of the turnover of the disease greatly. An incremental count of latently infected T4 cells was made under therapeutic simulation, and patients were found to fail to respond to HAART therapy in the presence of certain stimuli, such as opportunistic infections. In general, the dynamics of the model qualitatively matched clinical observations very closely, indicating that the model may have benefits in evaluating the efficacy of different drug therapy regimens and in the discovery of new monitoring markers and therapeutic schemes for the treatment of HIV-1 infection.

A viral infection model with a nonlinear infection rate is constructed based on empirical evidences. Qualitative analysis shows that there is a degenerate singular infection equilibrium. Furthermore, bifurcation of cusp-type with codimension two (i.e., Bogdanov-Takens bifurcation) is confirmed under appropriate conditions. As a result, the rich dynamical behaviors indicate that the model can display an Allee effect and fluctuation effect, which are important for making strategies for controlling the invasion of virus.

In this paper, we investigate a Leslie-type predator-prey model that incorporates prey harvesting and group defense, leading to a modified functional response. Our analysis focuses on the existence and stability of the system's equilibria, which are essential for the coexistence of predator and prey populations and the maintenance of ecological balance. We identify the maximum sustainable yield, a critical factor for achieving this balance. Through a thorough examination of positive equilibrium stability, we determine the conditions and initial values that promote the survival of both species. We delve into the system's dynamics by analyzing saddle-node and Hopf bifurcations, which are crucial for understanding the system transitions between various states. To evaluate the stability of the Hopf bifurcation, we calculate the first Lyapunov exponent and offer a quantitative assessment of the system's stability. Furthermore, we explore the Bogdanov-Takens (BT) bifurcation, a co-dimension 2 scenario, by employing a universal unfolding technique near the cusp point. This method simplifies the complex dynamics and reveals the conditions that trigger such bifurcations. To substantiate our theoretical findings, we conduct numerical simulations, which serve as a practical validation of the model predictions. These simulations not only confirm the theoretical results but also showcase the potential of the model for predicting real-world ecological scenarios. This in-depth analysis contributes to a nuanced understanding of the dynamics within predator-prey interactions and advances the field of ecological modeling. [ABSTRACT FROM AUTHOR]