AIM: To develop a mathematical model for the early detection of hepatocellular carcinoma (HCC) with a panel of serum proteins in combination with α-fetoprotein (AFP).METHODS: Serum levels of interleukin (I...AIM: To develop a mathematical model for the early detection of hepatocellular carcinoma (HCC) with a panel of serum proteins in combination with α-fetoprotein (AFP).METHODS: Serum levels of interleukin (IL)-8, soluble intercellular adhesion molecule-1 (sICAM-1), soluble tumor necrosis factor receptor II (sTNF-RII), proteasome, and β-catenin were measured in 479 subjects categorized into four groups: (1) HCC concurrent with hepatitis C virus (HCV) infection (n = 192); (2) HCV related liver cirrhosis (LC) (n = 96); (3) Chronic hepatitis C (CHC) (n = 96); and (4) Healthy controls (n = 95). The R package and different modules for binary and multi-class classifiers based on generalized linear models were used to model the data. Predictive power was used to evaluate the performance of the model. Receiver operating characteristic curve analysis over pairs of groups was used to identify the best cutoffs differentiating the different groups.RESULTS: We revealed mathematical models, based on a binary classifier, made up of a unique panel of serum proteins that improved the individual performance of AFP in discriminating HCC patients from patients with chronic liver disease either with or without cirrhosis. We discriminated the HCC group from the cirrhotic liver group using a mathematical model (-11.3 + 7.38 × Prot + 0.00108 × sICAM + 0.2574 × β-catenin + 0.01597 × AFP) with a cutoff of 0.6552, which achieved 98.8% specificity and 89.1% sensitivity. For the discrimination of the HCC group from the CHC group, we used a mathematical model [-10.40 + 1.416 × proteasome + 0.002024 × IL + 0.004096 × sICAM-1 + (4.251 × 10<sup>-4</sup>) × sTNF + 0.02567 × β-catenin + 0.02442 × AFP] with a cutoff 0.744 and achieved 96.8% specificity and 89.7% sensitivity. Additionally, we derived an algorithm, based on a binary classifier, for resolving the multi-class classification problem by using three successive mathematical model predictions of liver disease status.CONCLUSION: Our proposed mathematical model may be a useful method for the early detection of different statuses of liver disease co-occurring with HCV infection.展开更多
Radiation therapy is a longstanding cancer treatment. More recently, it has been demonstrated that radiation therapy(RT) elicits anti-cancer immune response. For this reason, there is a growing interest in combining R...Radiation therapy is a longstanding cancer treatment. More recently, it has been demonstrated that radiation therapy(RT) elicits anti-cancer immune response. For this reason, there is a growing interest in combining RT with immunotherapy, specifically with checkpoint inhibitors such as anti-CTLA-4 and anti-PDL1. In the present paper, we develop a mathematical model of combination therapy with RT and anti-PD-L1.The model is used to compare different schedules in clinical trials. Simulations of the model show that applying both RT and anti-PD-L1 at the same week has more benefits than applying them in separate adjacent weeks.Furthermore, applying anti-PD-L1 before RT has more benefits than applying RT before anti-PD-L1.展开更多
The search and development of anti-HIV drugs is currently one of the most urgent tasks of pharmacological studies. In this work, a quantitative structure-activity relationship （QSAR） model based on some new norm ind...The search and development of anti-HIV drugs is currently one of the most urgent tasks of pharmacological studies. In this work, a quantitative structure-activity relationship （QSAR） model based on some new norm indexes, was obtained to a series of more than 150 HEPT derivatives （1-[（2-hydroxyethoxy）methyl]-6-（phenylthio）thymine） to find their pEC50 （the required effective concentration to achieve 50% protection of MT-4 cells against the cytopathic effect of virus） and pCC50 （the required cytotoxic concentration to reduce visibility of 50% mock infected cell） activities. The model efficiencies were then validated using the leave-one-out cross validation （LOO-CV） and y- randomization test. Results indicated that this new model was efficient and could provide satisfactory results for prediction of pECso and pCC50 with the higher R2 train and the higher Rt2est. By using the leverage approach, the applicability domain of this model was further investigated and no response outlier was detected for HEFT derivatives involved in this work. Comparison results with reference methods demonstrated that this new method could result in significant improvements for predicting pEC50 and pCC50 of anti-HIV HEPT derivatives. Moreover, results shown in this present study suggested that these two absolutely different activities pECso and pCC50 of anti-HIV HEPT derivatives could be predicted well with a totally similar QSAR model, which indicated that this model mizht have the potential to be further utilized for other biological activities of HEFT derivatives.展开更多
In this article,we introduce a nonlinear Caputo-type snakebite envenoming model with memory.The well-known Caputo fractional derivative is used to generalize the previously presented integer-order model into a fractio...In this article,we introduce a nonlinear Caputo-type snakebite envenoming model with memory.The well-known Caputo fractional derivative is used to generalize the previously presented integer-order model into a fractionalorder sense.The numerical solution of the model is derived from a novel implementation of a finite-difference predictor-corrector(L1-PC)scheme with error estimation and stability analysis.The proof of the existence and positivity of the solution is given by using the fixed point theory.From the necessary simulations,we justify that the first-time implementation of the proposedmethod on an epidemicmodel shows that the scheme is fully suitable and time-efficient for solving epidemic models.This work aims to show the novel application of the given scheme as well as to check how the proposed snakebite envenoming model behaves in the presence of the Caputo fractional derivative,including memory effects.展开更多
基金Supported by National Cancer InstituteCairo University,Cairo,Egypt
文摘AIM: To develop a mathematical model for the early detection of hepatocellular carcinoma (HCC) with a panel of serum proteins in combination with α-fetoprotein (AFP).METHODS: Serum levels of interleukin (IL)-8, soluble intercellular adhesion molecule-1 (sICAM-1), soluble tumor necrosis factor receptor II (sTNF-RII), proteasome, and β-catenin were measured in 479 subjects categorized into four groups: (1) HCC concurrent with hepatitis C virus (HCV) infection (n = 192); (2) HCV related liver cirrhosis (LC) (n = 96); (3) Chronic hepatitis C (CHC) (n = 96); and (4) Healthy controls (n = 95). The R package and different modules for binary and multi-class classifiers based on generalized linear models were used to model the data. Predictive power was used to evaluate the performance of the model. Receiver operating characteristic curve analysis over pairs of groups was used to identify the best cutoffs differentiating the different groups.RESULTS: We revealed mathematical models, based on a binary classifier, made up of a unique panel of serum proteins that improved the individual performance of AFP in discriminating HCC patients from patients with chronic liver disease either with or without cirrhosis. We discriminated the HCC group from the cirrhotic liver group using a mathematical model (-11.3 + 7.38 × Prot + 0.00108 × sICAM + 0.2574 × β-catenin + 0.01597 × AFP) with a cutoff of 0.6552, which achieved 98.8% specificity and 89.1% sensitivity. For the discrimination of the HCC group from the CHC group, we used a mathematical model [-10.40 + 1.416 × proteasome + 0.002024 × IL + 0.004096 × sICAM-1 + (4.251 × 10<sup>-4</sup>) × sTNF + 0.02567 × β-catenin + 0.02442 × AFP] with a cutoff 0.744 and achieved 96.8% specificity and 89.7% sensitivity. Additionally, we derived an algorithm, based on a binary classifier, for resolving the multi-class classification problem by using three successive mathematical model predictions of liver disease status.CONCLUSION: Our proposed mathematical model may be a useful method for the early detection of different statuses of liver disease co-occurring with HCV infection.
基金supported by the Fundamental Research Funds for the Central Universities (Grant No. 19XNLG14)the Research Funds of Renmin University of ChinaNational Natural Science Foundation of China (Grant Nos. 11501568 and 11571364)
文摘Radiation therapy is a longstanding cancer treatment. More recently, it has been demonstrated that radiation therapy(RT) elicits anti-cancer immune response. For this reason, there is a growing interest in combining RT with immunotherapy, specifically with checkpoint inhibitors such as anti-CTLA-4 and anti-PDL1. In the present paper, we develop a mathematical model of combination therapy with RT and anti-PD-L1.The model is used to compare different schedules in clinical trials. Simulations of the model show that applying both RT and anti-PD-L1 at the same week has more benefits than applying them in separate adjacent weeks.Furthermore, applying anti-PD-L1 before RT has more benefits than applying RT before anti-PD-L1.
基金Supported by the National Natural Science Foundation of China(21306137)
文摘The search and development of anti-HIV drugs is currently one of the most urgent tasks of pharmacological studies. In this work, a quantitative structure-activity relationship （QSAR） model based on some new norm indexes, was obtained to a series of more than 150 HEPT derivatives （1-[（2-hydroxyethoxy）methyl]-6-（phenylthio）thymine） to find their pEC50 （the required effective concentration to achieve 50% protection of MT-4 cells against the cytopathic effect of virus） and pCC50 （the required cytotoxic concentration to reduce visibility of 50% mock infected cell） activities. The model efficiencies were then validated using the leave-one-out cross validation （LOO-CV） and y- randomization test. Results indicated that this new model was efficient and could provide satisfactory results for prediction of pECso and pCC50 with the higher R2 train and the higher Rt2est. By using the leverage approach, the applicability domain of this model was further investigated and no response outlier was detected for HEFT derivatives involved in this work. Comparison results with reference methods demonstrated that this new method could result in significant improvements for predicting pEC50 and pCC50 of anti-HIV HEPT derivatives. Moreover, results shown in this present study suggested that these two absolutely different activities pECso and pCC50 of anti-HIV HEPT derivatives could be predicted well with a totally similar QSAR model, which indicated that this model mizht have the potential to be further utilized for other biological activities of HEFT derivatives.
文摘In this article,we introduce a nonlinear Caputo-type snakebite envenoming model with memory.The well-known Caputo fractional derivative is used to generalize the previously presented integer-order model into a fractionalorder sense.The numerical solution of the model is derived from a novel implementation of a finite-difference predictor-corrector(L1-PC)scheme with error estimation and stability analysis.The proof of the existence and positivity of the solution is given by using the fixed point theory.From the necessary simulations,we justify that the first-time implementation of the proposedmethod on an epidemicmodel shows that the scheme is fully suitable and time-efficient for solving epidemic models.This work aims to show the novel application of the given scheme as well as to check how the proposed snakebite envenoming model behaves in the presence of the Caputo fractional derivative,including memory effects.
