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Background: Routine use of immunosuppressive agents in systemic lupus erythematosus (SLE) patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) potentially increases the risk of adverse outcomes. belimumab, a monoclonal antibody for the treatment of SLE, remains untested for its specific impact on coronavirus disease 2019 (COVID-19) symptoms in these patients. Here, this research investigated the effect of belimumab on COVID-19 symptoms in SLE patients infected with SARS-CoV-2. Methods: This study enrolled SLE patients who underwent treatment with belimumab. After thorough screening based on the inclusion and exclusion criteria, data pertaining to COVID-19 for both the participants and their cohabitants were obtained through telephone follow-up. The potential impact of belimumab on COVID-19 was evaluated by comparing COVID-19 symptoms and medication use across various groups to investigate the association between belimumab treatment and COVID-19 in SLE. Results: This study involved 123 SLE patients, of whom 89.4% tested positive for SARS-CoV-2. Among cohabitants of SLE patients, the SARS-CoV-2 positive rate was 87.2% (p = 0.543). Patients treated with belimumab exhibited a lower incidence of multiple COVID-19 symptoms than their cohabitating counterparts (p < 0.001). This protective effect was found to be partially related to the time of last belimumab administration. Among those with COVID-19, 30 patients opted to discontinue their anti-SLE drugs, and among them, 53% chose to discontinue belimumab. Discontinuing drugs did not increase the risk of hospitalization due to SARS-CoV-2 infection. Conclusion: This study concluded that treatment with belimumab did not increase susceptibility to COVID-19 and beneficially alleviated the symptoms of COVID-19. [ABSTRACT FROM AUTHOR]

We study a viral infection model incorporating both cell-to-cell infection and immune chemokines. Based on experimental results in the literature, we make a standing assumption that the cytotoxic T lymphocytes (CTL) will move toward the location with more infected cells, while the diffusion rate of CTL is a decreasing function of the density of infected cells. We first establish the global existence and ultimate boundedness of the solution via a priori energy estimates. We then define the basic reproduction number of viral infection R 0 and prove (by the uniform persistence theory, Lyapunov function technique and LaSalle invariance principle) that the infection-free steady state E 0 is globally asymptotically stable if R 0 < 1 . When R 0 > 1 , then E 0 becomes unstable, and another basic reproduction number of CTL response R 1 becomes the dynamic threshold in the sense that if R 1 < 1 , then the CTL-inactivated steady state E 1 is globally asymptotically stable; and if R 1 > 1 , then the immune response is uniform persistent and, under an additional technical condition the CTL-activated steady state E 2 is globally asymptotically stable. To establish the global stability results, we need to prove point dissipativity, obtain uniform persistence, construct suitable Lyapunov functions, and apply the LaSalle invariance principle. [ABSTRACT FROM AUTHOR]

It is imperative that resources are channelled towards programs that are efficient and cost effective in combating the spread of COVID-19, the disease caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). This study proposed and analyzed control strategies for that purpose. We developed a mathematical disease model within an optimal control framework that allows us to investigate the best approach for curbing COVID-19 epidemic. We address the following research question: what is the role of community compliance as a measure for COVID-19 control? Analyzing the impact of community compliance of recommended guidelines by health authorities—examples, social distancing, face mask use, and sanitizing—coupled with efforts by health authorities in areas of vaccine provision and effective quarantine—showed that the best intervention in addition to implementing vaccination programs and effective quarantine measures, is the active incorporation of individuals' collective behaviours, and that resources should also be directed towards community campaigns on the importance of face mask use, social distancing, and frequent sanitizing, and any other collective activities. We also demonstrated that collective behavioral response of individuals influences the disease dynamics; implying that recommended health policy should be contextualized. [ABSTRACT FROM AUTHOR]

Esophageal cancer is a highly malignant disease with poor prognosis. Despite recent advances in the study of esophageal cancer, there has been only limited improvement in the treatment and prognosis. N6-methyladenosine (m6A), a type of RNA modification, has been extensively investigated and is involved in many biological behaviors, including tumorigenesis and progression. Thus, more research on m6A modification may increase our understanding of esophageal cancer pathogenesis and provide potential targets. In our study, we integrated the public data of esophageal cancer from The Cancer Genome Atlas (TCGA) and Gene-Expression Omnibus (GEO) databases. Unsupervised clustering analysis was used to classify patients into different groups. Gene set variation analysis (GSVA) was performed in a nonparametric and unsupervised mode. We evaluated immune cell infiltration by single sample gene set enrichment analysis (ssGSEA). Differentially expressed genes (DEGs) among m6A clusters were identified using Empirical Bayesian approach. Both multivariate and univariate Cox regression models were used for prognostic analysis. We provided an overview of gene variation and expression of 23 m6A regulators in esophageal cancer, as well as their effects on survival. Based on the overall expression level of m6A regulators, patients were classified into three m6A clusters (A-C) with different immune cell infiltration abundance, gene expression signatures and prognosis. Among m6A clusters, we identified 206 DEGs, according to which patients were classified into 4 gene clusters (A-D). Quantitative m6A score was calculated for each patient based on those DEGs with significant impact on survival. The infiltration of all types of immune cells except type 2 T helper (Th2) cells were negatively correlated with m6A score. M6Acluster C exhibited the lowest m6A score, the most abundant immune cell infiltration, and the worst prognosis, suggesting an immune excluded phenotype. Consistently, gene cluster D with the lowest m6A score showed the worst prognosis. In short, patients with esophageal cancer showed different m6A modification patterns. Quantitative scoring indicated that patients with the lowest m6A score exhibited the most abundant immune cell infiltration and the poorest prognosis. This m6A scoring system is promising to assess m6A modification pattern, characterize immune infiltration and guide personalized treatment and prognostic prediction. [ABSTRACT FROM AUTHOR]

Since the beginning of the global pandemic of Coronavirus (SARS-COV-2), there has been many studies devoted to predicting the COVID-19 related deaths/hospitalizations. The aim of our work is to (1) explore the lagged dependence between the time series of case counts and the time series of death counts; and (2) utilize such a relationship for prediction. The proposed approach can also be applied to other infectious diseases or wherever dynamics in lagged dependence are of primary interest. Different from the previous studies, we focus on time-varying coefficient models to account for the evolution of the coronavirus. Using two different types of time-varying coefficient models, local polynomial regression models and piecewise linear regression models, we analyze the province-level data in Canada as well as country-level data using cumulative counts. We use out-of-sample prediction to evaluate the model performance. Based on our data analyses, both time-varying coefficient modeling strategies work well. Local polynomial regression models generally work better than piecewise linear regression models, especially when the pattern of the relationship between the two time series of counts gets more complicated (e.g., more segments are needed to portray the pattern). Our proposed methods can be easily and quickly implemented via existing R packages. [ABSTRACT FROM AUTHOR]

We describe the behaviour of solutions of a scalar Delay Differential Equation (DDE) with delay that periodically switches between two constant values. Such an equation arises naturally from structured vector populations involved in a range of vector-borne diseases spreading in a periodically varying environment. We examine if and how the two different time lags and the switching time influence the existence and patterns of periodic solutions. We pay particular attention to the patterns involving multi-cycles within the prime period of the periodic solutions. [ABSTRACT FROM AUTHOR]

Background and Objective: HP501 is a highly selective renal urate transporter 1 (URAT1) inhibitor that is being developed for the treatment of hyperuricemia and gout. The primary aim of the present study was to study the pharmacokinetic drug‒drug interactions (DDIs) of HP501, febuxostat, and colchicine in hyperuricemic patients. Methods: Hyperuricemic patients were randomly divided into group A, receiving HP501 40 mg once daily on days 1 and 4–10, and group B, receiving febuxostat 40 mg once daily on day 1 and HP501 40 mg plus febuxostat 40 mg on days 4–10. All patients received 0.5 mg colchicine once daily from day 4 to 12. Blood samples were collected for measurement of drug concentrations and serum uric acid (sUA) levels. Results: Coadministration of colchicine with HP501 or HP501 plus febuxostat did not affect steady-state exposure to colchicine. Coadministration of HP501 and febuxostat did not significantly change the pharmacokinetic profiles of either drug. Following multiple administrations of HP501 40 mg once daily for 7 days, the maximal percent sUA change from baseline in group A was − 24.77%. The coadministration of HP501 40 mg and febuxostat 40 mg in group B for 7 days resulted in a − 55.82% maximal sUA reduction from baseline, and all patients achieved the goal of sUA < 360 μmol/L. All adverse events (AEs) were either mild or moderate, and the most frequently reported AEs were diarrhea and elevated alanine aminotransferase (ALT) levels. Conclusions: The concomitant use of HP501, febuxostat, and colchicine did not produce clinically meaningful DDIs in terms of their pharmacokinetic properties. Clinical Trial Registration: No. CTR20212261 (http://www.chinadrugtrials.org.cn/) registered September 2021. [ABSTRACT FROM AUTHOR]

We represent the optimal control functions by neural networks and solve optimal control problems by deep learning techniques. Adjoint sensitivity analysis is applied to train the neural networks embedded in differential equations. This method can not only be applied in classic epidemic control problems, but also in epidemic forecasting, discovering unknown mechanisms, and the ideas behind can give new insights to traditional mathematical epidemiological problems. [ABSTRACT FROM AUTHOR]

We propose a coupled system of delay-algebraic equations to describe tick attaching and host grooming behaviors in the tick-host interface, and use the model to understand how this tick-host interaction impacts the tick population dynamics. We consider two critical state variables, the loads of feeding ticks on host and the engorged ticks on the ground for ticks in a particular development stage (nymphal stage) and show that the model as a coupled system of delay differential equation and an algebraic (integral) equation may have rich structures of equilibrium states, leading to multi-stability. We perform asymptotic analyses and use the implicit function theorem to characterize the stability of these equilibrium states, and show that bi-stability and quadri-stability occur naturally in several combinations of tick attaching and host grooming behaviours. In particular, we show that in the case when host grooming is triggered by the tick biting, the system will have three stable equilibrium states including the extinction state, and two unstable equilibrium states. In addition, the two nontrivial stable equilibrium states correspond to a low attachment rate and a large number of feeding ticks, and a high attachment rate and a small number of feeding ticks, respectively. [ABSTRACT FROM AUTHOR]

Introduction: Women are more likely than men to develop the chronic, progressive autoimmune disease known as rheumatoid arthritis (RA). Although there may be a complex interplay between sex-based differences and autoimmune dysfunction. Their function in RA is largely unknown, though. The purpose of this study was to pinpoint the crucial genes and metabolic pathways that control biological variations in RA between men and women. Methods: First, the Gene Expression Omnibus database's gene expression information for GSE39340 and GSE55457 was downloaded (GEO). R software was used to find each of the individually identified differentially expressed genes (DEGs) between the sexes. DEGs that overlapped were found. The interactions between the overlapping DEGs were then further examined using a protein-protein interaction (PPI) network. The Kyoto Encyclopedia of Genes and Genomes and Gene Ontology tools, respectively, were used to perform enrichment analyses. Results: According to our findings, there were 1169 DEGs that overlapped between RA males and females, comprising 845 up-regulated genes and 324 down-regulated genes. Ten hub genes, including PIK3R1, RAC1, HRAS, PTPN11, UQCRB, NDUFV1, EGF, UBA1, UBE2G1, and UBE2E1, were discovered in the PPI network. According to a functional enrichment analysis, these genes were primarily enriched in neurodegenerative illnesses, including various disease pathways, MAPK signaling, insulin signaling, and autophagy. Conclusion: The current data point to the possibility that the MAPK pathway and autophagy may be significant contributors to sex differences in RA. PTPN11, EGF, and UBA1 may be important genes linked to the gender development of RA and are anticipated to be therapeutic targets for the disease. Key Points • Our research point to the possibility that the MAPK pathway and autophagy may be significant contributors to sex differences in RA. • PTPN11, EGF, and UBA1 may be important genes linked to the gender development of RA and are anticipated to be therapeutic targets for the disease. • These findings may aid in the development of novel diagnostic and treatment techniques for RA in men and women. [ABSTRACT FROM AUTHOR]

We consider a scalar delay differential equation x ˙ (t) = - d x (t) + f ((1 - α) ρ x (t - τ) + α ρ x (t - 2 τ)) with an instant mortality rate d > 0 , the nonlinear Rick reproductive function f, a survival rate during all development stages ρ , and a proportion constant α ∈ [ 0 , 1 ] with which population undergoes a diapause development. We consider global continuation of a branch of periodic solutions locally generated through the Hopf bifurcation mechanism, and we establish the existence of periodic solutions with periods within (3 τ , 6 τ) for a wide range of parameter values. We show this existence of periodic solutions not only for the delay τ near the first critical value τ ∗ when a local Hopf bifurcation takes place near the positive equilibrium, but for all τ > τ ∗ . We obtain this (global) existence of periodic solutions by using the equivalent-degree based global Hopf bifurcation theory, coupled with an application of the Li–Muldowney technique to rule out periodic solutions with period 3 τ . We conduct some numerical simulations to illustrate that this global continuation is completely due to the diapause-delay since solutions of the delay differential equation with only normal development delay in the given biologically realistic range all converge to the positive equilibrium. [ABSTRACT FROM AUTHOR]

Objectives: Sjögren's syndrome (SS), a systemic autoimmune disorder, is characterized by dry mouth and eyes. However, SS pathogenesis is poorly understood. We performed bioinformatics analysis to investigate the potential targets and molecular pathogenesis of SS. Methods: Gene expression profiles (GSE157159) and methylation data (GSE110007) associated with SS patients were obtained from the Gene Expression Omnibus (GEO) database. Differentially methylated positions (DMPs) and differentially expressed genes (DEGs) were identified by the R package limma. The potential biological functions of DEGs were determined using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Key DMPs were selected by overlap and the shrunken centroid algorithm, and corresponding genes were identified as hub genes, with their diagnostic value assessed by receiver operating characteristic (ROC) curves. The potential molecular mechanisms of hub genes were analyzed by protein–protein interaction (PPI) networks and single-gene gene set enrichment analysis (GSEA). Peripheral blood mononuclear cells (PBMCs) were collected from control and SS patients at The Affiliated Hospital of Southwest Medical University and Dazhou Central Hospital. The mRNA levels of hub genes were verified by quantitative real-time polymerase chain reaction (qRT–PCR). Results: We identified 788 DMPs and 2457 DEGs between the two groups. Functional enrichment analysis suggested that the DEGs were significantly enriched in T cell activation, leukocyte cell–cell adhesion, and cytokine–cytokine receptor interaction. TSS200, TSS1500, and 1stExon were identified as highly enriched areas of differentially methylated promoter CpG islands (DMCIs). In total, 61 differentially methylated genes (DMGs) were identified by the overlap of 2457 DEGs and 507 genes related to DMPs (DMPGs), of which 21 genes located near TSS200, TSS1500, and 1stExon were selected. Then, three key DMPs and the corresponding hub genes (RUNX3, HLA-DPA1, and CD6) were screened by the shrunken centroid algorithm and calculated to have areas under the ROC curve of 1.000, 0.931, and 0.986, respectively, indicating good diagnostic value. The GSEA results suggested that all three hub genes were highly associated with the immune response. Finally, positive mRNA expression of the three hub genes in clinical SS samples was verified by qRT–PCR, consistent with the GSE157159 data. Conclusions: The identification of three hub genes provides novel insight into molecular mechanisms and therapeutic targets for SS. Key Points • Hub genes were screened by DNA methylation and transcriptome analyses. • The relative expression of hub genes in peripheral blood samples was verified by qRT–PCR. • HLA-DPA1 was correlated with the pathogenic mechanism of SS. [ABSTRACT FROM AUTHOR]

Widespread vaccination is necessary to minimize or halt the effects of many infectious diseases, including COVID-19. Stagnating vaccine uptake can prolong pandemics, raising the question of how we might predict, prevent, and correct vaccine hesitancy and unwillingness. In a multinational sample (N = 4,452) recruited from 13 countries that varied in pandemic severity and vaccine uptake (July 2021), we examined whether short-sighted decision-making as exemplified by steep delay discounting—choosing smaller immediate rewards over larger delayed rewards—predicts COVID-19 vaccination status. Delay discounting was steeper in unvaccinated individuals and predicted vaccination status over and above demographics or mental health. The results suggest that delay discounting, a personal characteristic known to be modifiable through cognitive interventions, is a contributing cause of differences in vaccine compliance. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a joint disorder that is associated with chondrocyte damage under inflammatory environment. Calycosin is an astragalus extract with potential anti-inflammatory and anti-tumor activities. The purpose of this research is to explore the activity and mechanism of calycosin in interleukin-1beta (IL-1β)-induced chondrocyte injury. In the present study, the targets of calycosin and OA were analyzed according to HERB, DisGeNet, String, GO terms, and KEGG pathway enrichment assays. Human primary chondrocytes were treated with calycosin, and stimulated with IL-1β. Cell viability was detected by CCK-8 assay. Cell apoptosis was investigated by flow cytometry, and caspase-3 activity analyses. Inflammation was analyzed according to inflammatory cytokines levels by enzyme-linked immunosorbent assay (ELISA). The proteins associated with extracellular matrix (ECM) degradation and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/forkhead box O1 (FoxO1) signaling pathways were measured using Western blotting. The results showed that total of 25 overlapping targets of calycosin against OA were predicted. These targets might drive the FoxO pathway. Calycosin alone induced little cytotoxicity to chondrocytes, and it alleviated IL-1β-induced viability inhibition, cell apoptosis, inflammatory cytokine secretion, and ECM degradation in chondrocytes. Calycosin repressed IL-1β-induced activation of the PI3K/AKT/FoxO1 signaling. Activation of the PI3K/AKT/FoxO1 signaling mitigated the suppressive effect of calycosin on chondrocyte apoptosis, inflammation, and ECM degradation induced by IL-1β. As a conclusion, calycosin prevents IL-1β-induced chondrocyte apoptosis, inflammation, and ECM degradation through inactivating the PI3K/AKT/FoxO1 pathway. [ABSTRACT FROM AUTHOR]

In the present paper, we aimed to determine the influence of various non-pharmaceutical interventions (NPIs) enforced during the first wave of COVID-19 across countries on the spreading rate of COVID-19 during the second wave. For this purpose, we took into account national-level climatic, environmental, clinical, health, economic, pollution, social, and demographic factors. We estimated the growth of the first and second wave across countries by fitting a logistic model to daily-reported case numbers, up to the first and second epidemic peaks. We estimated the basic and effective (second wave) reproduction numbers across countries. Next, we used a random forest algorithm to study the association between the growth rate of the second wave and NPIs as well as pre-existing country-specific characteristics. Lastly, we compared the growth rate of the first and second waves of COVID-19. The top three factors associated with the growth of the second wave were body mass index, the number of days that the government sets restrictions on requiring facial coverings outside the home at all times, and restrictions on gatherings of 10 people or less. Artificial intelligence techniques can help scholars as well as decision and policy-makers estimate the effectiveness of public health policies, and implement "smart" interventions, which are as efficacious as stringent ones. [ABSTRACT FROM AUTHOR]

Drive-through clinics have previously been utilized in vaccination efforts and are now being more widely adopted for COVID-19 vaccination in different parts of the world by offering many advantages including utilizing existing infrastructure, large daily throughput and enforcing social distancing by default. Successful, effective, and efficient drive-through facilities require a suitable site and keen focus on layout and process design. To demonstrate the role that high fidelity computer simulation can play in planning and design of drive-through mass vaccination clinics, we used multiple integrated discrete event simulation (DES) and agent-based modelling methods. This method using AnyLogic simulation software to aid in planning, design, and implementation of one of the largest and most successful early COVID-19 mass vaccination clinics operated by UCHealth in Denver, Colorado. Simulations proved to be helpful in aiding the optimization of UCHealth drive through mass vaccination clinic design and operations by exposing potential bottlenecks, overflows, and queueing, and clarifying the necessary number of supporting staff. Simulation results informed the target number of vaccinations and necessary processing times for different drive through station set ups and clinic formats. We found that modern simulation tools with advanced visual and analytical capabilities to be very useful for effective planning, design, and operations management of mass vaccination facilities. [ABSTRACT FROM AUTHOR]

Large data requirements are often the main hurdle in training neural networks. Convolutional neural network (CNN) classifiers in particular require tens of thousands of pre-labeled images per category to approach human-level accuracy, while often failing to generalized to out-of-domain test sets. The acquisition and labelling of such datasets is often an expensive, time consuming and tedious task in practice. Synthetic data provides a cheap and efficient solution to assemble such large datasets. Using domain randomization (DR), we show that a sufficiently well generated synthetic image dataset can be used to train a neural network classifier that rivals state-of-the-art models trained on real datasets, achieving accuracy levels as high as 88% on a baseline cats vs dogs classification task. We show that the most important domain randomization parameter is a large variety of subjects, while secondary parameters such as lighting and textures are found to be less significant to the model accuracy. Our results also provide evidence to suggest that models trained on domain randomized images transfer to new domains better than those trained on real photos. Model performance appears to remain stable as the number of categories increases. [ABSTRACT FROM AUTHOR]

We consider a coupled system of delay differential equations for a single-species tick population dynamics, assuming feeding adult ticks are distributed by their hosts in a spatially heterogeneous environment consisting of two patches where egg ticks produced will complete their life cycles with different, normal and diapause, developmental delays. We show that the mobility of adult tick host and the diapause developmental delay combined drive a synchronized oscillation in the total tick populations around a uniquely defined positive equilibrium, and this synchronization makes the oscillatory patterns much simpler in comparison with multi-peak oscillations exhibited in the absence of host mobility. [ABSTRACT FROM AUTHOR]

Understanding the effect of landscape characteristics on water quality can provide insight into mitigating water quality impairment. However, there is no consensus about the key controlling factors influencing water quality. This paper examined the combined effects of land use and topography on water quality across multi-scale, and identified the key controlling factors determining water quality variation in the headwater watershed of the Hengxi reservoir in Eastern China. Water quality impairment (WQI), expressed as a composite variable, was established to measure the overall water quality. We used the partial least squares (PLSR) method to explore the combination of landscape metrics and identify the key controlling factors. Results showed that the optimal PLSR model at 50-m, 100-m, and 150-m buffer scales and catchment scale explained 77%, 63%, 60%, and 56% of variability in WQI, respectively. At catchment scale, patch density, the percentage of paddy field, and hypsometric integral were the key controlling factors impacting water quality. At buffer scales, the slope gradient, the percentage of forest land, and topographic wetness index were more effectively determined WQI variation. Thus, the key controlling factors depend on spatial scales. Both spatial scales and corresponding key controlling factors should be considered in the adjustment of land use composition and planning of landscape configuration to better protect water quality. [ABSTRACT FROM AUTHOR]

The dissemination of one public hot event is usually affected by some related information, and the implication of co-propagation by different information is critical for the integrated analysis. To help in designing effective communication strategies during the whole event, we propose the cross-transmission susceptible-forwarding-immune (CT-SFI) model to describe the dynamics of co-propagation particularly with focus on the cross-transmission effects. This model is based on the forwarding quantity and takes into account the behavior that users may have a strong attraction or continuous attraction within or without an active time after contacting one information. Data fitting using the real data of Chinese Sina-microblog can accurately parameterize the model and parameter sensitivity analysis gives some strategies for co-propagation. [ABSTRACT FROM AUTHOR]

Purpose: Pubic symphysis diastasis with an incidence of approximately 20% in pelvic fractures is a severe lesion which needs to be treated properly. The objective of this retrospective study was to describe and evaluate the clinical and radiological outcomes including its advantages and limitations of this modified minimal invasive technique. Methods: Totally 29 patients with pubic symphysis diastasis, with or without posterior ring instability, were treated by modified pedicle screw–rod fixation (modified PSRF) between January 2010 and December 2016. The duration from injury to surgery, operation time, intraoperative blood loss as well as complications were recorded. During follow-up, the functional outcomes were assessed according to the Majeed evaluation criteria 1 year postoperatively. The evaluation of the postoperative reduction quality was carried out according to Matta criteria. Results: According to Tile classification, there were 9 cases of Type B1 underwent only anterior-modified PSRF and 20 cases of Type C1 experienced anterior-modified PSRF combined with posterior fixation. The duration from injury to operation, operation time and intraoperative blood loss were 3.27 days (range 1–6 days), 42.07 min (range 38–45 min), and 46.14 ml (range 40–55 ml). The results of reduction quality were rated as excellent in 16, good in 11 and fair in 2 based on Matta criteria. The Majeed functional scores ranged from 68 to 95 and there were excellent in 15, good in 12 and fair in 2. No patients experienced incision infection. Slight loosening of middle-two screws was verified during follow-up in one patient. Two patients underwent femoral nerve palsy. Irritation to the LFCN was detected in four patients. Conclusions: Modified PSRF can be performed as an alternative to manage pubic symphysis diastasis due to its merits of minimal invasive, less blood loss, less soft tissue injuries as well as shorter operation time, even with the early weight-bearing. Trial registration: Researchregistry3905. [ABSTRACT FROM AUTHOR]

Leflunomide (LEF) is a conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) for the treatment of rheumatoid arthritis. However, there are few reports on the comparison of efficacy between LEF alone and combined with other csDMARDs. Here, the efficacy and safety of LEF monotherapy (88) and combination (361) therapy groups were evaluated. After 3 months, there were no significant differences in 28-joint disease activity score (DAS28), health assessment questionnaire (HAQ), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) between the monotherapy and combination groups (all P > 0.05). According to the European League Against Rheumatism (EULAR) response criteria, it was found that the DAS28 response rates were similar in the two groups (P > 0.05). Besides, the two groups presented similar safety profiles. Subgroup analysis found that there was no difference in efficacy among the three combined therapies (LEF + methotrexate (MTX), LEF + hydroxychloroquine (HCQ), and LEF + MTX + HCQ) and LEF monotherapy. Furthermore, when the dose of LEF was less than 40 mg/day, no significant difference in efficacy was observed between low and high doses. Overall, these results indicated that low dose LEF monotherapy was not inferior to the combination therapy. [ABSTRACT FROM AUTHOR]

Public health interventions have been implemented to mitigate the spread of coronavirus disease 2019 (COVID-19) in Ontario, Canada; however, the quantification of their effectiveness remains to be done and is important to determine if some of the social distancing measures can be relaxed without resulting in a second wave. We aim to equip local public health decision- and policy-makers with mathematical model-based quantification of implemented public health measures and estimation of the trend of COVID-19 in Ontario to inform future actions in terms of outbreak control and de-escalation of social distancing. Our estimates confirm that (1) social distancing measures have helped mitigate transmission by reducing daily infection contact rate, but the disease transmission probability per contact remains as high as 0.145 and case detection rate was so low that the effective reproduction number remained higher than the threshold for disease control until the closure of non-essential business in the Province; (2) improvement in case detection rate and closure of non-essential business had resulted in further reduction of the effective control number to under the threshold. We predict the number of confirmed cases according to different control efficacies including a combination of reducing further contact rates and transmission probability per contact. We show that improved case detection rate plays a decisive role to reduce the effective reproduction number, and there is still much room in terms of improving personal protection measures to compensate for the strict social distancing measures. [ABSTRACT FROM AUTHOR]

We study the existence and uniqueness of mild and strict solutions for abstract neutral differential equations with state-dependent delay. Some examples related to partial neutral differential equations are presented. [ABSTRACT FROM AUTHOR]

Purpose: To radiographically characterize the relationship between inferior displacement of great tuberosity (GT) fracture and associated occult or minor displaced humeral neck fracture.Methods: Thirty patients with inferior displacement of the GT on the initial anterior-posterior (AP) view X-ray were included in this study. Twenty-four patients received further computed tomography (CT) scans. One patient with negative CT scans underwent MRI. Radiographic indexes included the cervico-diaphyseal angle, the distance of the inferior displacement of the GT fracture, the apex-tuberosity distance, and the direction of the GT shift on the 3D-CT scan. The measurement reliability was analyzed by calculating intra-class correlation (ICC) coefficients. The relationships between the parameters were revealed using Pearson correlation analysis.Results: In the 30 cases, humeral neck fractures were detected by AP view X-ray (6 cases), CT (23 cases), and MRI (1 case). The mean cervico-diaphyseal angle was 146.7° ± 8.9°. The mean inferior displacement of the GT fracture was 13.4 ± 5.9 mm. The mean apex-tuberosity distance was 11.8 ± 2.8 mm. Posterior/inferior displacement of the GT fractures was observed in 24 patients via CT scan. All the evaluated parameters presented correlations among methods, indicating intra-rater and inter-rater reliability. The Pearson correlation analysis revealed that inferior displacement of GT fracture was correlated with the cervico-diaphyseal angle (P < 0.05).Conclusion: The inferior displacement of GT fracture on AP view X-ray is a useful diagnostic clue for the early recognition of occult humeral neck fracture and may indicate the need for further CT/MRI examination. [ABSTRACT FROM AUTHOR]

We study the existence and nonexistence of traveling waves of diffusive epidemic models with general incidence rates. The model systems are non-monotone because of the intrinsic predator–prey interaction between the susceptible and infective compartments in epidemic systems. Moreover, the incidence rate may not be monotone in the infected population because social behaviors and collective activities may change in response to the prevalence of disease. To find positive traveling solutions of the non-monotone system with a non-monotone incidence function, we will construct a suitable convex set in a weighted function space, and then apply Schauder fixed point theorem. It turns out that the basic reproduction number of the corresponding ordinary differential equations plays an important role in the existence theory of traveling waves. Moreover, the critical wave speed can be explicitly obtained in terms of the diffusion coefficient, recovery rate and death rate for the infected group, and partial derivative of incidence function at the disease-free equilibrium. Finally, we prove that the positive traveling wave solution does not exist if the basic reproduction number is no more than one, or the wave speed is less than the critical value. [ABSTRACT FROM AUTHOR]

Ixodid ticks are acknowledged as one of the most important hematophagous arthropods because of their ability in transmitting a variety of tick-borne diseases. Mathematical models have been developed, based on emerging knowledge about tick ecology, pathogen epidemiology and their interface, to understand tick population dynamics and tick-borne diseases spread patterns. However, no serious effort has been made to model and assess the impact of host immunity triggered by tick feeding on the distribution of the tick population according to tick stages and on tick population extinction and persistence. Here, we construct a novel mathematical model taking into account the effect of host immunity status on tick population dynamics, and analyze the long-term behaviours of the model solutions. Two threshold values, R 11 and R 22 , are introduced to measure the reproduction ratios for the tick-host interaction in the absence and presence of host immunity. We then show that these two thresholds (sometimes under additional conditions) can be used to predict whether the tick population goes extinct ( R 11 < 1 ) and the tick population grows without bound ( R 22 > 1 ). We also prove tick permanence (persistence and boundedness of the tick population) and the existence of a tick persistence equilibrium if R 22 < 1 < R 11 . As the host species adjust their immunity to tick infestation levels, they form for the tick population an environment with a carrying capacity very much like that in logistic growth. Numerical results show that the host immune reactions decrease the size of the tick population at equilibrium and apparently reduce the tick-borne infection risk. [ABSTRACT FROM AUTHOR]

We revisit a previously established model for influenza transmission dynamics, in which antiviral treatment as a single containment strategy was administered within a specified window of opportunity for initiating treatment. We extend this model to a more general framework with age-of-infection dependent treatment rates. The resulting age structured model can be transformed into a closed system of delay differential equations, for which we perform a complete global stability analysis. By constructing suitable Lyapunov functions, we show that the effective reproduction number fully characterizes the possible outcomes of disease dynamics. Our results allow us to evaluate treatment strategies and examine the impact of treatment delays on the potential success of disease control. [ABSTRACT FROM AUTHOR]

Two or more groups with different initial opinions can develop into a consensus with appropriate inter- and intra group interactions and communication delay. Here we consider the case when zero is a semi-simple eigenvalue of the normalized connection matrix, and we expand the concept of consensus where opinions of all individual agents must converge to the common (consensus) value to the weak consensus where opinions are clustered and the consensus value is no longer a scalar constant but a vector in a certain consensus subspace. The linearity of the system enables us to adopt an argument of Atay, using the phase space decomposition in terms of the standard bilinear form for functional differential equations, to derive sharp conditions for the system to reach a weak consensus, and to calculate the consensus vector. This calculation also informs how the consensus value of the coupled systems depends on the consensus of the subgroups, initial conditions and communication delay. We also point out the challenge of extending these results to nonlinear versions of the opinion dynamical systems with delay. [ABSTRACT FROM AUTHOR]

Background and Objectives: Hydronidone is a novel pyridine derivative with therapeutic potential for hepatic fibrosis. The aim of this study was to investigate the safety, tolerability, and pharmacokinetics of hydronidone in healthy subjects. Effects of sex and food on hydronidone pharmacokinetics were also evaluated. Methods: A randomized, dose-escalating, first-in-human study was conducted in 88 subjects. Five cohorts of 34 subjects received a single dose of hydronidone capsules at 15-120 mg, and two cohorts of 12 subjects received 90 and 120 mg of hydronidone thrice daily for 7 days, and six subjects received 60 mg of hydronidone thrice daily for 28 days to assess the safety and tolerability. In 36 subjects, hydronidone pharmacokinetics were investigated following oral administration of single (30, 60, and 120 mg) and multiple (60 mg, thrice daily) doses of hydronidone. Results: Plasma concentrations of hydronidone and area under the concentration-time curve were found to be proportional to dose. Hydronidone was rapidly absorbed [median time to maximum plasma concentration ( t ) = 0.33-0.63 h] and cleared [terminal elimination half-life ( t ) = 1.72-3.10 h]. Pharmacokinetic parameters after multiple doses were similar to those after single dose. Food had a significant affect ( P < 0.01) on the extent and rate of absorption. No significant sex differences were noted for pharmacokinetic variables. Conclusion: Hydronidone was well tolerated and rapidly absorbed, and concomitant intake of food reduced rate and extent (about 20 %) of absorption in healthy volunteers. There was no accumulation following multiple doses of hydronidone. These results support a 60 mg thrice-daily regimen for management of hepatic fibrosis and further development of hydronidone (registered at ClinicalTrials.gov as ChiCTR-ONC-12002899). [ABSTRACT FROM AUTHOR]

The tolerability and pharmacokinetics of disodium folinate may vary with different races, and these variations might result in different outcomes. This study assessed the tolerability and pharmacokinetics of disodium folinate following single intravenous doses in healthy Chinese subjects, with gender factor also taken into account. Subjects were randomized to receive a single dose of disodium folinate at 20, 200, or 300 mg/m administered intravenously over a time period of 10 min. Sequential blood samples were collected at regular intervals over 24 h after dosing and were analyzed using a validated high-performance liquid chromatography (HPLC) method. Pharmacokinetic parameters, including C, AUC, t, V, and CL, were calculated using non-compartmental models. Tolerability was assessed by collecting adverse events (AEs) and monitoring vital signs, physical examinations, laboratory tests, and electrocardiograms. Following a single intravenous administration of disodium folinate 20, 200, and 300 mg/m, the mean (standard deviation) pharmacokinetic parameters were as follows: C = 5.18 (0.58), 47.80 (10.10), and 69.93 (9.72) µg/mL; AUC = 25.85 (3.36), 194.53 (30.18), and 355.26 (35.31) µg h/mL; AUC = 30.24 (6.19), 215.43 (27.34), and 417.88 (54.81) µg h/mL; t = 8.77 (2.57), 7.64 (1.81), and 9.08 (1.64) h; CL = 1.12 (0.18), 1.55(0.25), and 0.78 (0.09) L/h; V = 13.75 (2.61), 17.38 (6.44), and 10.05 (1.49) L, respectively. The mean C, AUC, and AUC increased in a dose-proportional manner. No significant differences in pharmacokinetic parameters were noted by gender. The most common AEs reported were mild redness at the injection site and neurological symptoms (headache, dizziness, and fatigue). [ABSTRACT FROM AUTHOR]

The main purpose is to develop novel analytical techniques and provide a comprehensive qualitative analysis of global dynamics for a state-dependent feedback control system arising from biological applications including integrated pest management. The model considered consists of a planar system of differential equations with state-dependent impulsive control. We characterize the impulsive and phase sets, using the phase portraits of the planar system and the Lambert W function to define the Poincaré map for impulsive point series defined in the phase set. The existence, local and global stability of an order-1 limit cycle and obtain sharp sufficient conditions for the global stability of the boundary order-1 limit cycle have been provided. We further examine the flip bifurcation related to the existence of an order-2 limit cycle. We show that the existence of an order-2 limit cycle implies the existence of an order-1 limit cycle. We derive sufficient conditions under which any trajectory initiating from a phase set will be free from impulsive effects after finite state-dependent feedback control actions, and we also prove that order- k ( $k\geq3$) limit cycles do not exist, providing a solution to an open problem in the integrated pest management community. We then investigate multiple attractors and their basins of attraction, as well as the interior structure of a horseshoe-like attractor. We also discuss implications of the global dynamics for integrated pest management strategy. The analytical techniques and qualitative methods developed in the present paper could be widely used in many fields concerning state-dependent feedback control. [ABSTRACT FROM AUTHOR]

In this work, CuCrO nanoparticles were successfully prepared by an improved hydrothermal process, and a resistive switching memory behavior with Ag/CuCrO/fluorine-doped tin oxide structure is demonstrated. Specially, the resistive switching memory characteristics can be controlled by white-light illumination. The device can maintain superior stability over 100 cycles with an OFF/ON-state resistance ratio of about 10 at room temperature. This study is useful for exploring the promising light-controlled resistive switching memory device in the development of resistive switching random-access memory. Graphical Abstract: We demonstrate a resistive switching device based on Ag/CuCrO/FTO structure, and the device shows light-controlled resistive switching memory characteristics.[Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

An immuno-epidemiological model of pathogen transmission is developed. This model incorporates two main features: (i) the epidemiological model includes within-host pathogen dynamics for an infectious disease, (ii) the susceptible individuals to the infection experience a series of exposures via the pathogen before becoming infectious. It is shown that this model leads naturally to a system of differential delay equations of the threshold type and that these equations can be transformed, in a biologically natural way, to differential equations with state-dependent delay. An interesting dynamical behavior of the model is the bistability phenomena, when the basic reproductive ratio $$R_{0}$$ is less than unity, which raises many new challenges to effective infection control. [ABSTRACT FROM AUTHOR]