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Abstract Ovarian cancer (OC) was the fifth leading cause of cancer death and the deadliest gynecological cancer in women. This was largely attributed to its late diagnosis, high therapeutic resistance, and a dearth of effective treatments. Clinical and preclinical studies have revealed that tumor-infiltrating CD8+T cells often lost their effector function, the dysfunctional state of CD8+T cells was known as exhaustion. Our objective was to identify genes associated with exhausted CD8+T cells (CD8TEXGs) and their prognostic significance in OC. We downloaded the RNA-seq and clinical data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. CD8TEXGs were initially identified from single-cell RNA-seq (scRNA-seq) datasets, then univariate Cox regression, the least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression were utilized to calculate risk score and to develop the CD8TEXGs risk signature. Kaplan–Meier analysis, univariate Cox regression, multivariate Cox regression, time-dependent receiver operating characteristics (ROC), nomogram, and calibration were conducted to verify and evaluate the risk signature. Gene set enrichment analyses (GSEA) in the risk groups were used to figure out the closely correlated pathways with the risk group. The role of risk score has been further explored in the homologous recombination repair deficiency (HRD), BRAC1/2 gene mutations and tumor mutation burden (TMB). A risk signature with 4 CD8TEXGs in OC was finally built in the TCGA database and further validated in large GEO cohorts. The signature also demonstrated broad applicability across various types of cancer in the pan-cancer analysis. The high-risk score was significantly associated with a worse prognosis and the risk score was proven to be an independent prognostic biomarker. The 1-, 3-, and 5-years ROC values, nomogram, calibration, and comparison with the previously published models confirmed the excellent prediction power of this model. The low-risk group patients tended to exhibit a higher HRD score, BRCA1/2 gene mutation ratio and TMB. The low-risk group patients were more sensitive to Poly-ADP-ribose polymerase inhibitors (PARPi). Our findings of the prognostic value of CD8TEXGs in prognosis and drug response provided valuable insights into the molecular mechanisms and clinical management of OC.

Abstract We aim to develop a nomogram to predict overt hepatic encephalopathy (OHE) after transjugular intrahepatic portosystemic shunt (TIPS) in patients with portal hypertension, according to demographic/clinical indicators such as age, creatinine, blood ammonia, indocyanine green retention rate at 15 min (ICG-R15) and percentage of Portal pressure gradient (PPG) decline. In this retrospective study, 296 patients with portal hypertension who received elective TIPS in Beijing Shijitan Hospital from June 2018 to June 2020 were included. These patients were randomly divided into a training cohort (n = 207) and a validation cohort (n = 89). According to the occurrence of OHE, patients were assigned to OHE group and non-OHE group. Both univariate and multivariate analyses were performed to determine independent variables for predicting OHE after TIPS. Accordingly, receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to compare the accuracy and superiority of a novel model with conventional Child–Pugh and MELD scoring model. Age (OR 1.036, 95% CI 1.002–1.070, p = 0.037), Creatinine (OR 1.011, 95% CI 1.003–1.019, p = 0.009), Blood ammonia (OR 1.025, 95% CI 1.006–1.044, p = 0.011), ICG-R15 (OR 1.030, 95% CI 1.009–1.052, p = 0.004) and Percentage decline in PPG (OR 1.068, 95% CI 1.029–1.109, p = 0.001) were independent risk factors for OHE after TIPS using multifactorial analysis. A nomogram was constructed using a well-fit calibration curve for each of these five covariates. When compared to Child–Pugh and MELD score, this new nomogram has a better predictive value (C-index = 0.828, 95% CI 0.761–0.896). Consistently, this finding was reproduceable in validation cohort and confirmed with DCA. A unique nomogram was developed to predict OHE after TIPS in patients with PHT, with a high prediction sensitivity and specificity performance than commonly applied scoring systems.

IntroductionIt is believed that ovarian cancer (OC) is the most deadly form of gynecological cancer despite its infrequent occurrence, which makes it one of the most salient public health concerns. Clinical and preclinical studies have revealed that intratumoral CD4+ T cells possess cytotoxic capabilities and were capable of directly killing cancer cells. This study aimed to identify the CD4+ conventional T cells-related genes (CD4TGs) with respect to the prognosis in OC.MethodsWe obtained the transcriptome and clinical data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. CD4TGs were first identified from single-cell datasets, then univariate Cox regression was used to screen prognosis-related genes, LASSO was conducted to remove genes with coefficient zero, and multivariate Cox regression was used to calculate riskscore and to construct the CD4TGs risk signature. Kaplan-Meier analysis, univariate Cox regression, multivariate Cox regression, time-dependent receiver operating characteristics (ROC), decision curve analysis (DCA), nomogram, and calibration were made to verify and evaluate the risk signature. Gene set enrichment analyses (GSEA) in risk groups were conducted to explore the tightly correlated pathways with the risk group. The role of riskscore has been further explored in the tumor microenvironment (TME), immunotherapy, and chemotherapy. A risk signature with 11 CD4TGs in OC was finally established in the TCGA database and furtherly validated in several GEO cohorts.ResultsHigh riskscore was significantly associated with a poorer prognosis and proven to be an independent prognostic biomarker by multivariate Cox regression. The 1-, 3-, and 5-year ROC values, DCA curve, nomogram, and calibration results confirmed the excellent prediction power of this model. Compared with the reported risk models, our model showed better performance. The patients were grouped into high-risk and low-risk subgroups according to the riskscore by the median value. The low-risk group patients tended to exhibit a higher immune infiltration, immune-related gene expression and were more sensitive to immunotherapy and chemotherapy.DiscussionCollectively, our findings of the prognostic value of CD4TGs in prognosis and immune response, provided valuable insights into the molecular mechanisms and clinical management of OC.

Epithelial ovarian cancer (EOC) is the leading killer among women with gynecologic malignancies. Homologous recombination deficiency (HRD) has attracted increasing attention due to its significant implication in the prediction of prognosis and response to treatments. In addition to the germline and somatic mutations of homologous recombination (HR) repair genes, to widely and deeply understand the molecular characteristics of HRD, we sought to screen the long non-coding RNAs (lncRNAs) with regard to HR repair genes and to establish a prognostic risk model for EOC. Herein, we retrieved the transcriptome data from the Genotype-Tissue Expression Project (GTEx) and The Cancer Genome Atlas (TCGA) databases. HR-related lncRNAs (HRRlncRNAs) associated with prognosis were identified by co-expression and univariate Cox regression analyses. The least absolute shrinkage and selection operator (LASSO) and multivariate stepwise Cox regression were performed to construct an HRRlncRNA risk model containing AC138904.1, AP001001.1, AL603832.1, AC138932.1, and AC040169.1. Next, Kaplan−Meier analysis, time-dependent receiver operating characteristics (ROC), nomogram, calibration, and DCA curves were made to verify and evaluate the model. Gene set enrichment analysis (GSEA), immune analysis, and prediction of the half-maximal inhibitory concentration (IC50) in the risk groups were also analyzed. The calibration plots showed a good concordance with the prognosis prediction. ROCs of 1-, 3-, and 5-year survival confirmed the well-predictive efficacy of this model in EOC. The risk score was used to divide the patients into high-risk and low-risk subgroups. The low-risk group patients tended to exhibit a lower immune infiltration status and a higher HRD score. Furthermore, consensus clustering analysis was employed to divide patients with EOC into three clusters based on the expression of the five HRRlncRNAs, which exhibited a significant difference in checkpoints’ expression levels and the tumor microenvironment (TME) status. Taken together, the results of this project supported that the five HRRlncRNA models might function as a biomarker and prognostic indicator with respect to predicting the PARP inhibitor and immune treatment in EOC.

The human immunodeficiency virus (HIV), as one of the most hazardous viruses, causes destructive effects on the human bodies’ immune system. Hence, an immense body of research has focused on developing antiretroviral therapies for HIV infection. In the current study, we propose a new control technique for a fractional-order HIV infection model. Firstly, a fractional model of the HIV model is investigated, and the importance of the fractional-order derivative in the modeling of the system is shown. Afterward, a type-2 fuzzy logic controller is proposed for antiretroviral therapy of HIV infection. The developed control scheme consists of two individual controllers and an aggregator. The optimal aggregator modifies the output of each individual controller. Simulations for two different strategies are conducted. In the first strategy, only reverse transcriptase inhibitor (RTI) is used, and the superiority of the proposed controller over a conventional fuzzy controller is demonstrated. Lastly, in the second strategy, both RTI and protease inhibitors (PI) are used simultaneously. In this case, an optimal type-2 fuzzy aggregator is also proposed to modify the output of the individual controllers based on optimal rules. Simulations results demonstrate the appropriate performance of the designed control scheme for the uncertain system.

Abstract We establish certain new fractional integral inequalities involving the Raina function for monotonicity of functions that are used with some traditional and forthright inequalities. Taking into consideration the generalized fractional integral with respect to a monotone function, we derive the Grüss and certain other associated variants by using well-known integral inequalities such as Young, Lah–Ribarič, and Jensen integral inequalities. In the concluding section, we present several special cases of fractional integral inequalities involving generalized Riemann–Liouville, k-fractional, Hadamard fractional, Katugampola fractional, ( k , s ) $(k,s)$ -fractional, and Riemann–Liouville-type fractional integral operators. Moreover, we also propose their pertinence with other related known outcomes.

Abstract Inequality theory provides a significant mechanism for managing symmetrical aspects in real-life circumstances. The renowned distinguishing feature of integral inequalities and fractional calculus has a solid possibility to regulate continuous issues with high proficiency. This manuscript contributes to a captivating association of fractional calculus, special functions and convex functions. The authors develop a novel approach for investigating a new class of convex functions which is known as an n-polynomial P $\mathcal{P}$ -convex function. Meanwhile, considering two identities via generalized fractional integrals, provide several generalizations of the Hermite–Hadamard and Ostrowski type inequalities by employing the better approaches of Hölder and power-mean inequalities. By this new strategy, using the concept of n-polynomial P $\mathcal{P}$ -convexity we can evaluate several other classes of n-polynomial harmonically convex, n-polynomial convex, classical harmonically convex and classical convex functions as particular cases. In order to investigate the efficiency and supremacy of the suggested scheme regarding the fractional calculus, special functions and n-polynomial P $\mathcal{P}$ -convexity, we present two applications for the modified Bessel function and q $\mathfrak{q}$ -digamma function. Finally, these outcomes can evaluate the possible symmetric roles of the criterion that express the real phenomena of the problem.

In statistical analysis, oftentimes a probability density function is used to describe the relationship between certain unknown parameters and measurements taken to learn about them. As soon as there is more than enough data collected to determine a unique solution for the parameters, an estimation technique needs to be applied such as “fractional calculus”, for instance, which turns out to be optimal under a wide range of criteria. In this context, we aim to present some novel estimates based on the expectation and variance of a continuous random variable by employing generalized Riemann-Liouville fractional integral operators. Besides, we obtain a two-parameter extension of generalized Riemann-Liouville fractional integral inequalities, and provide several modifications in the Riemann-Liouville and classical sense. Our ideas and obtained results my stimulate further research in statistical analysis.

We develop a new robust control scheme for a non-holonomic spherical robot. To this end, the mathematical model of a pendulum driven non-holonomic spherical robot is first presented. Then, a recurrent neural network-based robust nonsingular sliding mode control is proposed for stabilization and tracking control of the system. The designed recurrent neural network is applied to approximate compound disturbances, including external interferences and dynamic uncertainties. Moreover, the controller is designed in a way that avoids the singularity problem in the system. Another advantage of the proposed scheme is its ability for tracking control while there exists control input saturation, which is a serious concern in robotic systems. Based on the Lyapunov theorem, the stability of the closed-loop system has also been confirmed. Lastly, the performance of the proposed control technique for the uncertain system in the presence of an external disturbance, unknown input saturation, and dynamic uncertainties has been investigated. Also, the proposed controller has been compared with a Fuzzy-PID one. Simulation results show the effectiveness and superiority of the developed control technique.

Thermophoretic particle deposition is one of the most rudimentary processes for transferring small particles over a temperature gradient, and it is vital in aero-solution and electronic engineering. In the proposed model, it is intended to explore heat and mass transfer on double-diffusive electrically non-conducting Casson fluid in the two-dimensional flow past a stretching surface with thermophoretic particle deposition. An external magnetic field is subjected to a magnetic dipole. The analysis of Casson fluid along magnetic dipole represents the ferromagnetic fluid. As a consequence of the presence of ferrite particles, the fluid has magnetic properties and is thus a non-Newtonian Casson ferrofluid. Moreover, to enclose heat and mass transfer characteristics, thermal and solutal stratifications are also employed. An eminent bvp4c technique in MATLAB is incorporated to compute these ODEs numerically. Graphical representations of important parameters and their physical behavior are extensively analyzed. The Nusselt number, thermophoretic particle deposition velocity, and drag force coefficient are also addressed graphically. The findings demonstrate that as the values of thermophoretic coefficient and thermophoretic parameter increase, the mass transfer rate diminishes. Further, with the escalating values of the ferromagnetic interaction parameter, the velocity field is reduced but the opposite trend is seen for the thermal field.

In the present study, a vertically oriented rectangular-shaped enclosure with triangular shaped double fins filled with PCM was considered as a Latent Thermal Energy Storage (LTES) system. Nine different cases including one pure PCM, three nano-PCM (having different volume fractions), two porous-PCM (having different porosity values) and three nano/porous PCM were considered to conduct the investigation. The PCM material employed for investigations was lauric acid. The copper made porous media was assumed to have porosity values of 98% and 95%. The Al2O3 nano-particles with the volume fractions of 1%, 2% and 4% combined with Lauric acid were considered as nano-PCM. The results presented that the cases with nanoparticles volume fractions of 1% and 2% could improve the melting performance. However, the case with nanoparticle volume fraction of 4% deteriorated the melting performance. In the cases with individual usage of nano-PCM the best case was related to the case with the volume fraction of 1% and resulted in about 184s time-saving. It was found that individual usage of porous media could significantly improve the melting performance; however, adding nanoparticles to the cases with porous media, regardless of volume fraction of nanoparticles deteriorates the melting performance of PCM enclosure.

For a graph G, its variable sum exdeg index is defined as SEIaG=∑xy∈EGadx+ady, where a is a real number other than 1 and dx is the degree of a vertex x. In this paper, we characterize all trees on n vertices with first three maximum and first three minimum values of the SEIa index. Also, we determine all the trees of order n with given diameter d and having first three largest values of the SEIa index.

A novel approach to solve optimal control problems dealing simultaneously with fractional differential equations and time delay is proposed in this work. More precisely, a set of global radial basis functions are firstly used to approximate the states and control variables in the problem. Then, a collocation method is applied to convert the time-delay fractional optimal control problem to a nonlinear programming one. By solving the resulting challenge, the unknown coefficients of the original one will be finally obtained. In this way, the proposed strategy introduces a very tunable framework for direct trajectory optimization, according to the discretization procedure and the range of arbitrary nodes. The algorithm’s performance has been analyzed for several non-trivial examples, and the obtained results have shown that this scheme is more accurate, robust, and efficient than most previous methods.

Propofol is a neuroprotective anesthetic. Whether propofol can promote spinal cord injury repair by bone marrow mesenchymal stem cells remains poorly understood. We used rats to investigate spinal cord injury repair using bone marrow mesenchymal stem cell transplantation combined with propofol administration via the tail vein. Rat spinal cord injury was clearly alleviated; a large number of newborn non-myelinated and myelinated nerve fibers appeared in the spinal cord, the numbers of CM-Dil-labeled bone marrow mesenchymal stem cells and fluorogold-labeled nerve fibers were increased and hindlimb motor function of spinal cord-injured rats was markedly improved. These improvements were more prominent in rats subjected to bone marrow mesenchymal cell transplantation combined with propofol administration than in rats receiving monotherapy. These results indicate that propofol can enhance the therapeutic effects of bone marrow mesenchymal stem cell transplantation on spinal cord injury in rats.

The Resistance-Harary index of a connected graph G is defined as R H ( G ) = ∑ { u , v } ⊆ V ( G ) 1 r ( u , v ) , where r ( u , v ) is the resistance distance between vertices u and v in G. A graph G is called a unicyclic graph if it contains exactly one cycle and a fully loaded unicyclic graph is a unicyclic graph that no vertex with degree less than three in its unique cycle. Let U ( n ) and U ( n ) be the set of unicyclic graphs and fully loaded unicyclic graphs of order n, respectively. In this paper, we determine the graphs of U ( n ) with second-largest Resistance-Harary index and determine the graphs of U ( n ) with largest Resistance-Harary index.

The present study was done to determine whether kaempferol, a natural polyphenol of the flavonoid family, affects Epithelial-Mesenchymal Transition (EMT) in non-small cell lung cancer cells. Kaempferol not only inhibited cancer cell proliferation and migration in a dose-dependent manner but also modulated the expression of EMT-related proteins E-cadherin and vimentin which are indispensible to cellular motility, invasiveness and metastasis. These results indicate that kaempferol suppresses non-small cell lung cancer migration by modulating the expression of EMT proteins. Therefore, kaempferol may be useful as a potential anticancer agent for non-small cell lung cancer.

In the article, we present the sharp bounds for the Neuman mean NAG(a; b), NGA(a; b), NQA(a; b) and NAQ(a; b) in terms of the convex combinations of the arithmetic and one-parameter harmonic and contraharmonic means. As applications, we find several sharp inequalities for the first Seiffert, second Seiffert, Neuman-Sándor and logarithmic means. [ABSTRACT FROM AUTHOR]

The aim of the present study was to examine and assess contrast-enhanced ultrasound in the early diagnosis of acute radiation-induced liver injury in a rat model. Sixty female rats were used, with 50 rats being utilized to produce an animal model of liver injury with a single dose of stereotactic X-ray irradiation of 20 Gy. Ten rats from the injury group and 2 rats from the control group were randomly selected on days 3, 7, 14, 21 and 28, and examined by contrast-enhanced ultrasound and histopathology of liver specimens. The rats were divided into four groups: the normal control group, mild, moderate, and severe radioactive liver injury groups based on the histopathological examination results. Hepatic artery arriving time (HAAT) and hepatic vein arriving time (HVAT) were recorded, and hepatic artery to vein transit time (HA-HVTT) was calculated. The time-intensity curve of liver parenchyma, the time to peak (TTP) and peak intensity (PI) were also obtained. Significant differences were observed between liver injury and control groups for PI and HA-HVTT (P<0.05). PI and HA-HVTT were shorter in the severe liver injury group compared to the mild and moderate liver injury groups (P<0.05). Compared to the control group, higher TTP was recorded in all the liver injury groups (P<0.05), and the highest TTP level was observed in the severe liver injury group compared to the mild or moderate group (P<0.05). However, no significant difference was observed between the mild and moderate groups for PI, HA-HVTT and TTP. In conclusion, the results showed that contrast-enhanced ultrasonography is useful for an earlier diagnosis in a rat model of acute radiation-induced liver injury. [ABSTRACT FROM AUTHOR]

In this paper, we give the explicit formulas for the Neuman means NAH, NHA, NAC, and NCA, and present the best possible upper and lower bounds for these means in terms of the combinations of harmonic mean H, arithmetic mean A, and contraharmonic mean C. [ABSTRACT FROM AUTHOR]