Threshold dynamics of a reaction-advection-diffusion schistosomiasis epidemic model with seasonality and spatial heterogeneity.

Most water-borne disease models ignore the advection of water flows in order to simplify the mathematical analysis and numerical computation. However, advection can play an important role in determining the disease transmission dynamics. In this paper, we investigate the long-term dynamics of a periodic reaction-advection-diffusion schistosomiasis model and explore the joint impact of advection, seasonality and spatial heterogeneity on the transmission of the disease. We derive the basic reproduction number R 0 and show that the disease-free periodic solution is globally attractive when R 0 < 1 whereas there is a positive endemic periodic solution and the system is uniformly persistent in a special case when R 0 > 1 . Moreover, we find that R 0 is a decreasing function of the advection coefficients which offers insights into why schistosomiasis is more serious in regions with slow water flows.

PrEP Intervention in the Mitigation of HIV/AIDS Epidemics in China via a Data-Validated Age-Structured Model.

Antiretroviral-based pre-exposure prophylaxis (PrEP) treatment offers a new opportunity for protecting humans against HIV and disrupting current HIV prevention systems. However, implementing this preventive measure has been difficult due to its high cost. In this paper, we propose an age-structured model that incorporates infection ages, HAART (highly active antiretroviral therapy), and PrEP intervention. We investigate the qualitative behavior of the model and find a threshold parameter (the basic reproduction number) that determines the asymptotic stability of equilibria. We validate the model and estimate the parameters by confronting the actual HIV/AIDS data from 2004 to 2018 in China using MCMC (Markov Chain Monte Carlo) method. Furthermore, we investigate the PrEP intervention strategy by using incremental cost-effectiveness and average cost-effectiveness. Our work suggests that PrEP intervention based on the infection characteristics of different age groups can be an effective strategy to eradicate HIV/AIDS epidemics in China.

Low-intensity focused ultrasound ameliorates depression-like behaviors associated with improving the synaptic plasticity in the vCA1-mPFC pathway.

It is of great social significance and clinical value to explore new effective treatments for depression. Low-intensity focused ultrasound stimulation (LIFUS) has been indicated to have notable neuroprotective effects on depression. However, little is known about how different strategies of LIFUS affect the therapeutic effect. Therefore, the purpose of this study is to investigate whether the effects of LIFUS on depression-like behaviors are associated with the intensity and the underlying mechanisms. We established the depression rats model using the chronic unpredictable stress (CUS) and applied the LIFUS with high/low intensity (Ispta = 500 and 230 mW/cm2, respectively) to the left medial prefrontal cortex (mPFC) after CUS. We found that two intensities of LIFUS both could significantly improve depression-like behaviors to a comparable degree. We further found that theta oscillation synchronization and synaptic functional plasticity in the hippocampal vCA1-mPFC pathway were significantly improved by chronic LIFUS which mainly due to the alternation of synaptic structural plasticity and the expression of post-synaptic proteins in the mPFC. These results suggest that LIFUS ameliorates the depression-like behaviors associated with improving the synaptic plasticity in the vCA1-mPFC pathway. Our study provides preclinical evidence and a theoretical basis for applying LIFUS for depression treatment.

Spatial and temporal dynamics of SARS-CoV-2: Modeling, analysis and simulation.

A reaction-diffusion viral infection model is formulated to characterize the infection process of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a heterogeneous environment. In the model, the viral production, infection and death rates of compartments are given by the general functions. We consider the well-posedness of the solution, derive the basic reproduction number R 0 , discuss the global stability of uninfected steady state and explore the uniform persistence for the model. We further propose a spatial diffusion SARS-CoV-2 infection model with humoral immunity and spatial independent coefficients, and analyze the global attractivity of uninfected, humoral inactivated and humoral activated equilibria which are determined by two dynamical thresholds. Numerical simulations are performed to illustrate our theoretical results which reveal that diffusion, spatial heterogeneity and incidence types have evident impact on the SARS-CoV-2 infection process which should not be neglected for experiments and clinical treatments.

An epidemic-economic model for COVID-19.

In this paper, we propose a new mathematical model to study the epidemic and economic consequences of COVID-19, with a focus on the interaction between the disease transmission, the pandemic management, and the economic growth. We consider both the symptomatic and asymptomatic infections and incorporate the effectiveness of disease control into the respective transmission rates. Meanwhile, the progression of the pandemic and the evolution of the susceptible, infectious and recovered population groups directly impact the mitigation and economic development levels. We fit this model to the reported COVID-19 cases and unemployment rates in the US state of Tennessee, as a demonstration of a real-world application of the modeling framework.

From Policy to Prediction: Forecasting COVID-19 Dynamics Under Imperfect Vaccination.

Understanding the joint impact of vaccination and non-pharmaceutical interventions on COVID-19 development is important for making public health decisions that control the pandemic. Recently, we created a method in forecasting the daily number of confirmed cases of infectious diseases by combining a mechanistic ordinary differential equation (ODE) model for infectious classes and a generalized boosting machine learning model (GBM) for predicting how public health policies and mobility data affect the transmission rate in the ODE model (Wang et al. in Bull Math Biol 84:57, 2022). In this paper, we extend the method to the post-vaccination period, accordingly obtain a retrospective forecast of COVID-19 daily confirmed cases in the US, and identify the relative influence of the policies used as the predictor variables. In particular, our ODE model contains both partially and fully vaccinated compartments and accounts for the breakthrough cases, that is, vaccinated individuals can still get infected. Our results indicate that the inclusion of data on non-pharmaceutical interventions can significantly improve the accuracy of the predictions. With the use of policy data, the model predicts the number of daily infected cases up to 35 days in the future, with an average mean absolute percentage error of [Formula: see text], which is further improved to [Formula: see text] if combined with human mobility data. Moreover, the most influential predictor variables are the policies of restrictions on gatherings, testing and school closing. The modeling approach used in this work can help policymakers design control measures as variant strains threaten public health in the future.

A Hypothesis-Free Bridging of Disease Dynamics and Non-pharmaceutical Policies.

Accurate prediction of the number of daily or weekly confirmed cases of COVID-19 is critical to the control of the pandemic. Existing mechanistic models nicely capture the disease dynamics. However, to forecast the future, they require the transmission rate to be known, limiting their prediction power. Typically, a hypothesis is made on the form of the transmission rate with respect to time. Yet the real form is too complex to be mechanistically modeled due to the unknown dynamics of many influential factors. We tackle this problem by using a hypothesis-free machine-learning algorithm to estimate the transmission rate from data on non-pharmaceutical policies, and in turn forecast the confirmed cases using a mechanistic disease model. More specifically, we build a hybrid model consisting of a mechanistic ordinary differential equation (ODE) model and a gradient boosting model (GBM). To calibrate the parameters, we develop an "inverse method" that obtains the transmission rate inversely from the other variables in the ODE model and then feed it into the GBM to connect with the policy data. The resulting model forecasted the number of daily confirmed cases up to 35 days in the future in the USA with an averaged mean absolute percentage error of 27%. It can identify the most informative predictive variables, which can be helpful in designing improved forecasters as well as informing policymakers.

Improved Antimicrobial Ability of Dressings Containing Berberine Loaded Cellulose Acetate/Hyaluronic Acid Electrospun Fibers for Cutaneous Wound Healing.

An urgent problem in nursing care is the rising threat of cutaneous wound infections caused by harmful bacteria. In this study, we fabricated a series of cellulose acetate-hyaluronic acid (CA/HA) electrospun fibers loaded with berberine (BBR) using the electrospinning method to determine their antimicrobial performance and potential in in vivo skin wound dressing applications. The BBR-loaded CA/HA electrospun fibers (CA/HA/BBR) were analyzed using scanning electron and Fourier transform infrared microscopies; moreover, their mechanical properties were examined. The analyses demonstrated an average fiber diameter of 502 ± 50 nm; the tensile strength, Young's modulus, and break elongation of CA/HA electrospun fibers were approximately 3.23 ± 0.08 MPa, 17.5 ± 0.03 MPa, and 28.4%, respectively, whereas these values for CA/HA/BBR electrospun fibers were 238 ± 39 nm and 2.99 ± 0.05 MPa, 12.3 ± 0.04 MPa, and 47.8%, respectively. Antimicrobial evaluation of the CA/HA/BBR electrospun fibers demonstrated that the dressings made from these fibers exhibited greater antimicrobial efficacy (>95%) against Staphylococcus aureus and Escherichia coli when compared to that made from CA/HA (>80%) electrospun fibers. In vitro experiments showed that BBR loaded CA/HA electrospun fiber scaffolds have highly enhanced cell viability (>99) and proliferation of L929 fibroblastic cells after 7 days of incubation. In addition, in vivo evaluations in rats showed that the as-fabricated CA/HA/BBR bandage decreased wound size; moreover, it had accelerated healing ability (>95%) and collagen development with increasing treatment duration. These results showed that the addition of BBR enhanced the bioactivity of the dressing without damaging its physical characteristics. Thus, nanostructured dressing made of CA/HA/BBR electrospun fibers has excellent potency for tissue repair in nursing care.

Modeling Rabies Transmission in Spatially Heterogeneous Environments via [Formula: see text]-diffusion.

Rabies among dogs remains a considerable risk to humans and constitutes a serious public health concern in many parts of the world. Conventional mathematical models for rabies typically assume homogeneous environments, with a standard diffusion term for the population of rabid animals. It has recently been recognized, however, that spatial heterogeneity plays an important role in determining spatial patterns of rabies and the cost-effectiveness of vaccinations. In this paper, we develop a spatially heterogeneous dog rabies model by using the [Formula: see text]-diffusion equation, where [Formula: see text] reflects the way individual dogs make movement decisions in the underlying random walk. We numerically investigate the dynamics of the model in three diffusion cases: homogeneous, city-wild, and Gaussian-type. We find that the initial conditions affect whether traveling waves or epizootic waves can be observed. However, different initial conditions have little impact on steady-state solutions. An "active" interface is observed between city and wild regions, with a "ridge" on the city side and a "valley" on the wild side for the infectious dog population. In addition, the progressing speed of epizootic waves changes in heterogeneous environments. It is impossible to eliminate rabies in the entire spatial domain if vaccination is focused only in the city region or only in the wild region. When a seasonal transmission is incorporated, the dog population size approaches a positive time-periodic spatially heterogeneous state eventually.

Integrated Genome-Wide Methylation and Expression Analyses Reveal Key Regulators in Osteosarcoma.

Osteosarcoma (OS) is one of the most common types of primary bone tumors in early adolescence with unsatisfied prognosis. Aberrant DNA methylation had been demonstrated to be related to tumorigenesis and progression of multiple cancers and could serve as the potential biomarkers for the prognosis of human cancers. In conclusion, this study identified 18 downregulated hypomethylation genes and 52 upregulated hypomethylation genes in OS by integrating the analysis the GSE97529 and GSE42572 datasets. Bioinformatics analysis revealed that OS-specific methylated genes were involved in regulating multiple biological processes, including chemical synaptic transmission, transcription, response to drug, and regulating immune response. KEGG pathway analysis showed that OS-specific methylated genes were associated with the regulation of Hippo, cAMP calcium, MAPK, and Wnt signaling pathways. By analyzing R2 datasets, this study showed that the dysregulation of these OS-specific methylated genes was associated with the metastasis-free survival time in patients with OS, including CBLN4, ANKMY1, BZW1, KRTCAP3, GZMB, KRTDAP, LY9, PFKFB2, PTPN22, and CLDN7. This study provided a better understanding of the molecular mechanisms underlying the progression and OS and novel biomarkers for the prognosis of OS.

JQ1, a bromodomain inhibitor, suppresses Th17 effectors by blocking p300-mediated acetylation of RORγt.

BACKGROUND AND PURPOSE: Th17 cells play critical roles in chronic inflammation, including fibrosis. Histone acetyltransferase p300, a bromodomain-containing protein, acetylates RORγt and promotes Th17 cell development. The bromodomain inhibitor JQ1 was shown to alleviate Th17-mediated pathologies, but the underlying mechanism remains unclear. We hypothesized that JQ1 suppresses the response of Th17 cells by impairing p300-mediated acetylation of RORγt. EXPERIMENTAL APPROACH: The effect of JQ1 on p300-mediated acetylation of RORγt was investigated in HEK293T (overexpressing Flag-p300 and Myc-RORγt) and human Th17 cells through immunoprecipitation and western blotting. To determine the regions of p300 responsible for JQ1-mediated suppression of HAT activity, we performed HAT assays on recombinant p300 fragments with/without the bromodomain, after exposure to JQ1. Additionally, the effect of JQ1 on p300-mediated acetylation of RORγt and Th17 cell function was verified in vivo, using murine Schistosoma-induced fibrosis models. Liver injury was assessed by histopathological examination and measurement of serum enzyme levels. Expression of Th17 effectors was detected by qRT-PCR, whereas IL-17- and RORγt-positive granuloma cells were detected by FACS. KEY RESULTS: JQ1 impaired p300-mediated RORγt acetylation in human Th17 and HEK293T cells. JQ1 failed to suppress the acetyltransferase activity of p300 fragments lacking the bromodomain. JQ1 treatment attenuated Schistosoma-induced fibrosis in mice, by inhibiting RORγt acetylation and IL-17 expression. CONCLUSIONS AND IMPLICATIONS: JQ1 impairs p300-mediated RORγt acetylation, thus reducing the expression of RORγt target genes, including Th17-specific cytokines. JQ1-mediated inhibition of p300 acetylase activity requires the p300 bromodomain. Strategies targeting p300 may provide new therapeutic approaches for controlling Th17-related diseases.

Role of the Pumilio gene in the reproductive system of Schistosoma japonicum.

The elimination of schistosomiasis, a parasitic disease caused by Schistosoma and a major source of morbidity and mortality in developing countries, faces serious challenges. Although the pumilio protein regulates the reproductive organ development in many species, its role in Schistosoma japonicum is unknown. Thus, this study investigated the function of pumilio in S. japonicum reproduction. The complete coding sequences of S. japonicum Pumilio1 (SjPum1) and SjPum2 genes were cloned and characterized. The full-length open-reading frame SjPum1 (2613 nucleotides) and SjPum2 (4479 nucleotides) genes were obtained. Bioinformatics analysis showed that those genes belonged to the PUF (pumilio and FBF) family. Quantitative polymerase chain reaction analyses revealed that SjPum1 and SjPum2 were differentially expressed throughout the S. japonicum life cycle and were highly expressed in reproductive organs. In situ hybridization results showed that mRNA expression of SjPum2 was higher than that of SjPum1 in the ovary and testis. Knocking down SjPum2 using RNA interference techniques to explore potential reproductive functions showed that compared with the control (untransfected or scrambled mRNA-transfected) worms, the morphology of both male and female reproductive organs was altered, the number of eggs produced by paired females was significantly decreased, and the transcription levels of caspase 3 and caspase 7 genes related to apoptosis were significantly increased. The transcription level of Nanos1 gene which related to reproduction was also significantly increased. Therefore, SjPum2 may play a role in the reproductive development of S. japonicum.

The Emerging Role of lncRNAs in Spinal Cord Injury.

Spinal cord injury (SCI) is a highly debilitating disease and is increasingly being recognized as an important global health priority. However, the mechanisms underlying SCI have not yet been fully elucidated, and effective therapies for SCI are lacking. Long noncoding RNAs (lncRNAs), which form a major class of noncoding RNAs, have emerged as novel targets for regulating several physiological functions and mediating numerous neurological diseases. Notably, gene expression profile analyses have demonstrated aberrant changes in lncRNA expression in rats or mice after traumatic or nontraumatic SCI. LncRNAs have been shown to be associated with multiple pathophysiological processes following SCI including inflammation, neural apoptosis, and oxidative stress. They also play a crucial role in the complications associated with SCI, such as neuropathic pain. At the same time, some lncRNAs have been found to be therapeutic targets for neural stem cell transplantation and hydrogen sulfide treatment aimed at alleviating SCI. Therefore, lncRNAs could be promising biomarkers for the diagnosis, treatment, and prognosis of SCI. However, further researches are required to clarify the therapeutic effects of lncRNAs on SCI and the mechanisms underlying these effects. In this study, we reviewed the current progress of the studies on the involvement of lncRNAs in SCI, with the aim of drawing attention towards their roles in this debilitating condition.

R0 and sensitivity analysis of a predator-prey model with seasonality and maturation delay.

Coexistence and seasonal fluctuations of predator and prey populations are common and well documented in ecology. Under what conditions can predators coexist with prey in a seasonally changing environment? What factors drive long-term population cycles of some predator and prey species? To answer these questions, we investigate an improved predator-prey model based on the Rosenzweig-MacArthur [1] model. Our model incorporates seasonality and a predator maturation delay, leading to a system of periodic differential equations with a time delay. We define the basic reproduction ratio R0 and show that it is a threshold parameter determining whether the predators can coexist with the prey. We show that if R0 < 1, then the prey population has seasonal variations and the predator population goes extinct. If R0 > 1, then the prey and the predators coexist and fluctuate seasonally. As an example, we study a Daphnia-algae system and explore possible mechanisms for seasonal population cycles. Our numerical simulations indicate that seasonal Daphnia-algae cycles are attributed to seasonality rather than Daphnia maturation delay or Daphnia-algae interaction. The Daphnia maturation delay, the amplitude of algae growth rate and the amplitude of the carrying capacity are found to affect the amplitude of cycles and average population levels. Our sensitivity analysis shows that R0 is most sensitive to Daphnia death rate.

Regional climate affects salmon lice dynamics, stage structure and management.

Regional variation in climate can generate differences in population dynamics and stage structure. Where regional differences exist, the best approach to pest management may be region-specific. Salmon lice are a stage-structured marine copepod that parasitizes salmonids at aquaculture sites worldwide, and have fecundity, development and mortality rates that depend on temperature and salinity. We show that in Atlantic Canada and Norway, where the oceans are relatively cold, salmon lice abundance decreases during the winter months, but ultimately increases from year to year, while in Ireland and Chile, where the oceans are warmer, the population size grows monotonically without any seasonal declines. In colder regions, during the winter the stage structure is dominated by the adult stage, which is in contrast to warmer regions where all stages are abundant year round. These differences translate into region-specific recommendations for management: regions with slower population growth have lower critical stocking densities, and regions with cold winters have a seasonal dependence in the timing of follow-up chemotherapeutic treatments. Predictions of our salmon lice model agree with empirical data, and our approach provides a method to understand the effects of regional differences in climate on salmon lice dynamics and management.

Modeling the Potential Role of Engineered Symbiotic Bacteria in Malaria Control.

Recent experimental study suggests that the engineered symbiotic bacteria Serratia AS1 may provide a novel, effective and sustainable biocontrol of malaria. These recombinant bacteria have been shown to be able to rapidly disseminate throughout mosquito populations and to efficiently inhibit development of malaria parasites in mosquitoes in controlled laboratory experiments. In this paper, we develop a climate-based malaria model which involves both vertical and horizontal transmissions of the engineered Serratia AS1 bacteria in mosquito population. We show that the dynamics of the model system is totally determined by the vector reproduction ratio [Formula: see text], and the basic reproduction ratio [Formula: see text]. If [Formula: see text], then the mosquito-free state is globally attractive. If [Formula: see text] and [Formula: see text], then the disease-free periodic solution is globally attractive. If [Formula: see text] and [Formula: see text], then the positive periodic solution is globally attractive. Numerically, we verify the obtained analytic result and evaluate the effects of releasing the engineered Serratia AS1 bacteria in field by conducting a case study for Douala, Cameroon. We find that ideally, by using Serratia AS1 alone, it takes at least 25 years to eliminate malaria from Douala. This implies that continued long-term investment is needed in the fight against malaria and confirms the necessity of integrating multiple control measures.

Threshold Dynamics of a Temperature-Dependent Stage-Structured Mosquito Population Model with Nested Delays.

Mosquito-borne diseases remain a significant threat to public health and economics. Since mosquitoes are quite sensitive to temperature, global warming may not only worsen the disease transmission case in current endemic areas but also facilitate mosquito population together with pathogens to establish in new regions. Therefore, understanding mosquito population dynamics under the impact of temperature is considerably important for making disease control policies. In this paper, we develop a stage-structured mosquito population model in the environment of a temperature-controlled experiment. The model turns out to be a system of periodic delay differential equations with periodic delays. We show that the basic reproduction number is a threshold parameter which determines whether the mosquito population goes to extinction or remains persistent. We then estimate the parameter values for Aedes aegypti, the mosquito that transmits dengue virus. We verify the analytic result by numerical simulations with the temperature data of Colombo, Sri Lanka where a dengue outbreak occurred in 2017.

A climate-based malaria model with the use of bed nets.

Insecticide-treated bed nets (ITNs) are among the most important and effective intervention measures against malaria. In order to investigate the impact of bed net use on disease control, we formulate a periodic vector-bias malaria model incorporating the juvenile stage of mosquitoes and the use of ITNs. We derive the vector reproduction ratio [Formula: see text] and the basic reproduction ratio [Formula: see text]. We show that the global dynamics of the model is completely determined by these two reproduction ratios. More precisely, the mosquito-free periodic solution is globally attractive if [Formula: see text]; the unique disease-free periodic solution is globally attractive if [Formula: see text] and [Formula: see text]; and the model admits a unique positive periodic solution and it is globally attractive if [Formula: see text] and [Formula: see text]. Numerically, we study the malaria transmission case in Port Harcourt, Nigeria. Our findings show that the use of ITNs has a positive effect on reducing [Formula: see text], and that malaria may be eliminated from this area if over 75% of the human population were to use ITNs. The simulation about the long term behavior of solutions has good agreement with the obtained analytic result. Moreover, we find that the ignorance of the vector-bias effect may result in underestimation of the basic reproduction ratio [Formula: see text]. Another notable result is that the infection risk would be underestimated if the basic reproduction ratio [Formula: see text] of the time-averaged autonomous system were used.

A Malaria Transmission Model with Temperature-Dependent Incubation Period.

Malaria is an infectious disease caused by Plasmodium parasites and is transmitted among humans by female Anopheles mosquitoes. Climate factors have significant impact on both mosquito life cycle and parasite development. To consider the temperature sensitivity of the extrinsic incubation period (EIP) of malaria parasites, we formulate a delay differential equations model with a periodic time delay. We derive the basic reproduction ratio [Formula: see text] and establish a threshold type result on the global dynamics in terms of [Formula: see text], that is, the unique disease-free periodic solution is globally asymptotically stable if [Formula: see text]; and the model system admits a unique positive periodic solution which is globally asymptotically stable if [Formula: see text]. Numerically, we parameterize the model with data from Maputo Province, Mozambique, and simulate the long-term behavior of solutions. The simulation result is consistent with the obtained analytic result. In addition, we find that using the time-averaged EIP may underestimate the basic reproduction ratio.

Littoral cell angioma of the spleen: sonographic-pathologic comparison.

OBJECTIVES: The purpose of this study was to evaluate the sonographic and pathologic features of littoral cell angioma of the spleen in 7 patients. METHODS: The sonographic appearance in 7 cases of littoral cell angioma confirmed by surgical pathologic examination was retrospectively reviewed. All underwent color Doppler imaging. Two underwent contrast-enhanced sonography. The sonographic appearance was compared with pathologic findings. RESULTS: Splenic lesions were solitary in 5 cases and multiple in 2 cases. The masses ranged from 10 to 64 mm in maximum diameter. Five hypoechoic and 2 hyperechoic lesions on grayscale sonography corresponded to few and multiple blood-filled spaces on pathologic examination, respectively. Four hypovascular lesions, 1 hypervascular lesion, and the other 2 hypervascular lesions full of color flow signals on color Doppler imaging corresponded to few, several, and multiple arteries on pathologic examination. On contrast-enhanced sonography, 1 hypervascular lesion full of color flow signals showed homogeneous hyperenhancement for 8 minutes during the arterial and parenchymal phases. One hypovascular lesion showed inhomogeneous isoenhancement transiently during the arterial phase and became hypoechoic later. CONCLUSIONS: Littoral cell angioma is a primary vascular splenic neoplasm with variable features on grayscale sonography and color Doppler imaging as well as contrast-enhanced sonography. The sonographic appearance of littoral cell angioma mainly depends on the type and number of tumor vessels.