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Background: It remains unclear whether addition of docetaxel to the combination of a platinum and fluoropyrimidine could provide more clinical benefits than doublet chemotherapies in the perioperative treatment for locally advanced gastric/gastro-esophageal junction (LAG/GEJ) cancer in Asia. In this randomized, phase 2 study, we assessed the efficacy and safety of perioperative docetaxel plus oxaliplatin and S-1 (DOS) versus oxaliplatin plus S-1 (SOX) in LAG/GEJ adenocarcinoma patients. Methods: Patients with cT3–4 Nany M0 G/GEJ adenocarcinoma were randomized (1:1) to receive 4 cycles of preoperative DOS or SOX followed by D2 gastrectomy and another 4 cycles of postoperative chemotherapy. The primary endpoint was major pathological response (MPR). Results: From Aug, 2015 to Dec, 2019,154 patients were enrolled and 147 patients included in final analysis, with a median age of 60 (26–73) years. DOS resulted in significantly higher MPR (25.4 vs. 11.8%, P = 0.04). R0 resection rate, the 3-year PFS and 3-year OS rates were 78.9 vs. 61.8% (P = 0.02), 52.3 vs. 35% (HR 0.667, 95% CI: 0.432–1.029, Log rank P = 0.07) and 57.5 vs. 49.2% (HR 0.685, 95% CI: 0.429–1.095, Log rank P = 0.11) in the DOS and SOX groups, respectively. Patients who acquired MPR experienced significantly better survival. DOS had similar tolerance to SOX. Conclusions: Perioperative DOS improved MPR significantly and tended to produce longer PFS compared to SOX in LAG/GEJ cancer in Asia, and might be considered as a preferred option for perioperative chemotherapy and worth further investigation. [ABSTRACT FROM AUTHOR]

Point processes are probabilistic tools for modelling event data. While there exists a fast-growing literature on the relationships between point processes, how such relationships connect to causal effects remains unexplored. In the presence of unmeasured confounders, parameters from point process models do not necessarily have causal interpretations. We propose an instrumental variable method for causal inference with point process treatment and outcome. We define causal quantities based on potential outcomes and establish nonparametric identification results with a binary instrumental variable. We extend the traditional Wald estimation to deal with point process treatment and outcome, showing that it should be performed after a Fourier transform of the intention-to-treat effects on the treatment and outcome, and thus takes the form of deconvolution. We refer to this approach as generalized Wald estimation and propose an estimation strategy based on well-established deconvolution methods. [ABSTRACT FROM AUTHOR]

The activation, by residual stress, of the fast portion of rotational motion of single fluorescent probe molecules inside a polymer thin film near its glass transition temperature is studied at a single molecular level. Spin-casted poly n-butyl methacrylate thin films without thermal annealing are chosen as the model system and single molecule fluorescence defocused microscopy is adopted as the method. The rotational motion of the probes under residual stress is found to be more activated than that under mere thermal activation, and the kinetic energy exhibits a monotonic increase with the stress strength. A rough linear dependence of rotational kinetic energy at low stress is found, yielding the value of characteristic volume for the residual stress to activate the motion of the probes. The values of the volume are close to the van der Waals volume of the probes, indicating that the activation of the fast dynamics by residual stress is localized. The activation effect is weakened and vanishes at or above the glass transition temperature due to stress relaxation. The effect is also absent at temperatures far below Tg due to the frozen molecular motion with a much higher activation energy. [ABSTRACT FROM AUTHOR]

Two‐stage randomized experiments become an increasingly popular experimental design for causal inference when the outcome of one unit may be affected by the treatment assignments of other units in the same cluster. In this paper, we provide a methodological framework for general tools of statistical inference and power analysis for two‐stage randomized experiments. Under the randomization‐based framework, we consider the estimation of a new direct effect of interest as well as the average direct and spillover effects studied in the literature. We provide unbiased estimators of these causal quantities and their conservative variance estimators in a general setting. Using these results, we then develop hypothesis testing procedures and derive sample size formulas. We theoretically compare the two‐stage randomized design with the completely randomized and cluster randomized designs, which represent two limiting designs. Finally, we conduct simulation studies to evaluate the empirical performance of our sample size formulas. For empirical illustration, the proposed methodology is applied to the randomized evaluation of the Indian National Health Insurance Program. An open‐source software package is available for implementing the proposed methodology. [ABSTRACT FROM AUTHOR]

The dynamic behavior of a new financial system with diffusion effect and two delays is studied. The local stability of equilibrium is studied by analyzing the corresponding characteristic equation and developing the crossing curve method. Hopf bifurcation curves are obtained by three procedures and the critical value of delay of Hopf bifurcation is obtained. By using the central manifold theorem and the normal form theory of partial differential equations, the normal form of Hopf bifurcation with two delays is derived, and the bifurcation direction and the stability of periodic solution are determined. The numerical simulations not only verify these theoretical results, but also show that double Hopf bifurcation may occur and the two delays play a key role in chaos suppression. This study has important theoretical value of innovation and practical value in the macro-economic system. [ABSTRACT FROM AUTHOR]

Background: SOX (oxaliplatin and S1, every 3 weeks) is one of the most common first-line chemotherapy for advanced or metastatic G/GEJ (gastric or gastroesophageal junction) cancer in Asia, but it has noticeable hematological and neurological toxicity. In China, the majority of gastric cancer patients are middle-aged and elderly with poor tolerance to 3-weekly chemotherapy. Therefore, we aimed to assess efficacy and safety of biweekly SOX for Chinese advanced G/GEJ cancer patients aged ≥ 60 years as the first-line treatment in a single arm phase 2 study.Methods: Oxaliplatin was administered intravenously on day 1 at 85 mg/m2. S-1 was given at 80, 100 or 120 mg/day, depending on the body surface area (< 1.25 m2, 1.25 to < 1.5 m2, or ≥ 1.5 m2), twice daily, on day 1-10, every 2 weeks. The primary endpoint was objective response rate (ORR), and the secondary endpoints included progression free survival (PFS), overall survival (OS), disease control rate (DCR), duration of response (DOR) and safety.Results: Between May 2016 and Sep 2018, 42 patients were enrolled. The median follow-up was 43.6 months. The ORR and DCR were 52.4% and 85.7%, respectively. The median PFS was 4.6 months (95%CI 2.486-6.714), and the median OS was 11.1 months (95%CI 8.001-14.199). The most common treatment-related adverse events (TRAEs) of any grade included thrombocytopenia (59.5%), neutropenia (57.1%), appetite loss (57.1%) and nausea (54.8%). Only two patients suffered from grade 3 TRAEs (4.8%), including neutropenia (1 patient, [2.4%]) and diarrhea (1 patient, [2.4%]). No ≥ grade 4 TRAEs occurred.Conclusions: Biweekly SOX seemed to have favorable tolerance without compromising the efficacy as the first-line therapy in Chinese elderly patients aged ≥ 60 years with advanced G/GEJ cancer.Trial Registration: ClinicalTrials.gov ID: NCT04694404 (5/1/2021). This study was approved by the Ethical Committee of National Cancer Center/ National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, (17-048/1303). [ABSTRACT FROM AUTHOR]

To investigate the joint effects of diffusion and multiple delays, a toxin producing phytoplankton–zooplankton system with cross-diffusion is studied and two-parameter bifurcation analysis is carried out. Firstly, for the delay-free system, the stability of equilibria, existence of solutions and priori bound are given. The globally asymptotic stability of equilibrium is investigated for the two situations with or without the diffusion terms. The linear stability analyses show that the cross-diffusion is a key mechanism for Turing instability to occur and Turing instability interval becomes larger with increasing cross diffusion coefficient. Secondly, the focus is on the effects of delays on the system including persistence, stability and Hopf bifurcation. The sufficient conditions for the diffusion system with delays to remain persistent are given. Under certain conditions, the boundary equilibrium is globally asymptotically stable. By analyzing the distribution of roots of the characteristic equation, using the crossing curve methods, the stable changes of positive equilibrium in two-delay plane are obtained. Explicit algorithm is derived for the properties of the bifurcating periodic solutions by normal form theory and the center manifold theorem for partial functional differential equations. Finally, numerical simulations confirm the correctness of theoretical analyses and find that double Hopf bifurcation may occur. [ABSTRACT FROM AUTHOR]

Dictionary learning has gradually attracted attention due to its powerful feature representation ability. However, the time-shift property of collected signals hinders the recognition of various bearing states. In addition, existing dictionary learning methods are mostly designed based on a single domain, while common data fusion methods used in data-driven cannot be directly extended to dictionary learning. In this paper, a novel adaptive generalized domain data fusion-driven kernel sparse representation classification method (AGDFDK-SRC) is proposed. First, to avoid the effect of the time-shift property on dictionary learning, a class-specific kernel sub-dictionary learning method is proposed, by which the non-linear signal data is mapped into high-dimensional feature space via a kernel trick. Second, the class-specific kernel sub-dictionaries are learned by kernel K-singular value decomposition in a data-driven manner. Then, an adaptive generalized domain data fusion strategy is developed for dictionary learning, which implements data fusion of multiple domain signals to enhance the feature mining ability and representation ability of the learned dictionary. Finally, a kernel sparse classification method is designed to achieve intelligent bearing fault diagnosis. Two bearing datasets are exploited to verify the recognition performance of AGDFDK-SRC, indicating that the AGDFDK-SRC obtains superior average classification accuracies of 98.23% and 99.50%, respectively. [ABSTRACT FROM AUTHOR]

In this paper, a phytoplankton and zooplankton relationship system with two delays is investigated whose coefficients are related to one of the two delays. Firstly, the dynamic behaviors of the system with one delay are given and the stability of positive equilibrium and the existence of periodic solutions are obtained. Using the fact that the system may occur, the stable switching phenomenon is verified. Under certain conditions, the periodic solutions will exist in a wide range as the delay gets away from critical values. Fixing the delay τ in the stable interval, it is revealed that the effect of τ 1 can also cause the vibration of system. This explains that two delays play an important role in the oscillation behavior of the system. Furthermore, using the crossing curve methods, the stable changes of the positive equilibrium in two-delays plane are given, which generalizes the results of systems for which the coefficients do not depend on delay. Some numerical simulations are provided to verify the theoretical results. [ABSTRACT FROM AUTHOR]

In many social science experiments, subjects often interact with each other and as a result one unit's treatment influences the outcome of another unit. Over the last decade, a significant progress has been made toward causal inference in the presence of such interference between units. Researchers have shown that the two-stage randomization of treatment assignment enables the identification of average direct and spillover effects. However, much of the literature has assumed perfect compliance with treatment assignment. In this article, we establish the nonparametric identification of the complier average direct and spillover effects in two-stage randomized experiments with interference and noncompliance. In particular, we consider the spillover effect of the treatment assignment on the treatment receipt as well as the spillover effect of the treatment receipt on the outcome. We propose consistent estimators and derive their randomization-based variances under the stratified interference assumption. We also prove the exact relationships between the proposed randomization-based estimators and the popular two-stage least squares estimators. The proposed methodology is motivated by and applied to our own randomized evaluation of India's National Health Insurance Program (RSBY), where we find some evidence of spillover effects. The proposed methods are implemented via an open-source software package. for this article, including a standardized description of the materials available for reproducing the work, are available as an online supplement. [ABSTRACT FROM AUTHOR]

In this paper, a planktonic resource–consumer system with two delays is investigated and the coefficients depend on τ one of the two delays. Firstly, the property of solution and the existence of equilibrium are given. The dynamical analysis of the system including stability and Hopf bifurcation by using the delays as parameters is carried out. Both the single delay and two delays can cause the system to produce Hopf bifurcation and the stable switching phenomena may exist. Furthermore, using the crossing curve methods, we obtain the stable changes of equilibrium in two-delay parameter plane, which generalizes the results of the system that the coefficients do not depend on delay. Furthermore, the numerical simulation results show that the theoretical analyses are correct when the delays change. [ABSTRACT FROM AUTHOR]

Background: Capecitabine plus oxaliplatin (XELOX) as adjuvant therapy for gastric cancer (GC) reduces cancer recurrence and improves survival. S‐1 plus oxaliplatin (SOX) is well‐tolerated and effective against advanced GC, and also be used widely in adjuvant treatment. However, data comparing SOX and XELOX as adjuvant treatments are lacking. Method: Data on treatment modalities, adverse events, recurrence and metastasis were collected from 180 patients with stage II and III GC, who received SOX or XELOX after D2 gastrectomy between January 2012 and December 2015, and analyzed retrospectively. The primary endpoint was 3‐year disease‐free survival (DFS) rate. Results: Median follow was 52.9 months; 3‐year DFS rate and overall survival (OS) rate were 75.2% and 67.6% (P = 0.359) and 81.2% and 83.3% (P = 0.77) in the SOX and XELOX groups, respectively. There was no significant difference in peritoneal metastasis rates in the SOX and XELOX groups (8.6% vs 15%, respectively; P = 0.232). Compound recurrent disease was associated with significantly shorter OS. Multivariate analysis identified metastatic lymph node ratio (LNR) as an independent prognostic factor for OS (P = 0.036; hazard ratio = 2.875; 95% confidence interval, 1.069–7.729); the LNR ≥17% group had inferior 3‐year OS rate to the LNR <17% group (P = 0.001). The incidence of grades 3 and 4 adverse events was similar in both groups; however, grade ≥2 hand–foot syndrome was significantly less frequent in the SOX group (P = 0.01). Conclusion: SOX has similar survival benefits to XELOX and is well‐tolerated in Chinese patients with GC following D2 gastrectomy. [ABSTRACT FROM AUTHOR]

Instrumental variable methods can identify causal effects even when the treatment and outcome are confounded. We study the problem of imperfect measurements of the binary instrumental variable, treatment and outcome. We first consider nondifferential measurement errors, that is, the mismeasured variable does not depend on other variables given its true value. We show that the measurement error of the instrumental variable does not bias the estimate, that the measurement error of the treatment biases the estimate away from zero, and that the measurement error of the outcome biases the estimate toward zero. Moreover, we derive sharp bounds on the causal effects without additional assumptions. These bounds are informative because they exclude zero. We then consider differential measurement errors, and focus on sensitivity analyses in those settings. [ABSTRACT FROM AUTHOR]

In this paper, the system of describing the interactions between poisonous phytoplankton and zooplankton is presented. It focuses on the effects of two delays on the dynamic behavior of the system. At first, the properties of solutions including positivity and boundedness are given. Next, the stability of equilibria and the existence of local Hopf bifurcation are established when delays change and cross some threshold values. Especially, the existence of global periodic solutions is discussed when the two delays are equal. Furthermore, the implicit algorithm is derived for deciding the properties of the branching periodic solutions by using center manifold theory. Some numerical simulations are performed for supporting the theoretical results. Finally, some conclusions are given. [ABSTRACT FROM AUTHOR]

We begin by congratulating Yixin Wang and David Blei for their thought-provoking article that opens up a new research frontier in the field of causal inference. The authors directly tackle the challenging question of how to infer causal effects of many treatments in the presence of unmeasured confounding. We expect their article to have a major impact by further advancing our understanding of this important methodological problem. This commentary has two goals. We first critically review the deconfounder method and point out its advantages and limitations. We then briefly consider three possible ways to address some of the limitations of the deconfounder method. [ABSTRACT FROM AUTHOR]

Mediation analysis is popular in examining the extent to which the effect of an exposure on an outcome is through an intermediate variable. When the exposure is subject to misclassification, the effects estimated can be severely biased. In this paper, when the mediator is binary, we first study the bias on traditional direct and indirect effect estimates in the presence of conditional non-differential misclassification of a binary exposure. We show that in the absence of interaction, the misclassification of the exposure will bias the direct effect towards the null but can bias the indirect effect in either direction. We then develop an EM algorithm approach to correcting for the misclassification, and conduct simulation studies to assess the performance of the correction approach. Finally, we apply the approach to National Center for Health Statistics birth certificate data to study the effect of smoking status on the preterm birth mediated through pre-eclampsia. [ABSTRACT FROM AUTHOR]

• Mass transfer coefficient of oxygen can be measured by circulating bubble in 30 s. • The reactive mass transfer coefficient is of the order 10−4 m s−1 in turbulent flow. • The enhancement factor of the oxidation reaction is between 1.8 and 3. • The bubble and liquid Reynolds numbers in the mass transfer are elucidated. A non-intrusive measurement method was used to quantify the mass transfer between an oxygen bubble (with a spherical equivalent diameter in the range 2–4 mm) and the turbulent sodium sulfite solution in which the bubble was driven to circulate. The variations of the position, size, and velocity of the single bubble with time were derived from the images recorded by a high-speed camera, and the average reactive mass transfer coefficients were calculated from the reduction of the volume of the bubble. The enhancement factors under various flow conditions caused by the catalyzed chemical reaction were provided. The flow field in the chamber was measured by 2D particle image velocimetry (PIV). The single-phase instantaneous flow field was compared with the multi-phase flow field in terms of the effect of the single bubble. A correlation of the bubble Sherwood number with the bubble Reynolds number was obtained under different liquid Reynolds numbers. We found that the slip velocity has a high capacity to keep the bubble surface mobile. Both the bubble Reynolds number based on the bubble slip velocity and liquid Reynolds number contributed to the mass transfer in the turbulent chamber. [ABSTRACT FROM AUTHOR]

In this paper, a class of chaotic finance system with double delayed feedback control is investigated. Firstly, the stability of equilibrium and the existence of periodic solutions are discussed when delays change and cross some threshold value. Then the properties of the branching periodic solutions are given by using center manifold theory. Further, we give an example and numerical simulation, which implies that chaotic behavior can be transformed into a stable equilibrium or a stable periodic solution. Also, we give the local sensitivity analysis of parameters on equilibrium. [ABSTRACT FROM AUTHOR]

A toxin-producing phytoplankton and zooplankton system is investigated. Considering that zooplankton can be harvested for food in some bodies of water, the harvesting term is introduced to zooplankton population. Firstly, from the ordinary differential equation (ODE) system, we obtain the global asymptotic stability of equilibrium and optimal capture problem. Secondly, based on the ODE system, the diffusion term is introduced and the global asymptotic stability of the steady state solution is obtained. As a result, the diffusion cannot affect the global asymptotic stability of equilibrium, and Turing instability cannot occur. Once again, a delayed differential equation (DDE) system is put forward. The global asymptotic stability of boundary equilibrium and the existence of local Hopf bifurcation at positive equilibrium are discussed. Furthermore, it is proved that there exists at least one positive periodic solution as delay varies in some region by using the global Hopf result of Wu for functional differential equations. Lastly, some numerical simulations are carried out for supporting the theoretical analyses and the positive impacts of harvesting effort, and the release rate of toxin is given. The unstable interval of the positive equilibrium becomes smaller and smaller with the increase of harvesting effort or the release rate of toxin. [ABSTRACT FROM AUTHOR]

The matched-pairs design enables researchers to efficiently infer causal effects from randomized experiments. In this paper, we exploit the key feature of the matched-pairs design and develop a sensitivity analysis for missing outcomes due to truncation by death, in which the outcomes of interest (e.g., quality of life measures) are not even well defined for some units (e.g., deceased patients). Our key idea is that if 2 nearly identical observations are paired prior to the randomization of the treatment, the missingness of one unit's outcome is informative about the potential missingness of the other unit's outcome under an alternative treatment condition. We consider the average treatment effect among always-observed pairs (ATOP) whose units exhibit no missing outcome regardless of their treatment status. The naive estimator based on available pairs is unbiased for the ATOP if 2 units of the same pair are identical in terms of their missingness patterns. The proposed sensitivity analysis characterizes how the bounds of the ATOP widen as the degree of the within-pair similarity decreases. We further extend the methodology to the matched-pairs design in observational studies. Our simulation studies show that informative bounds can be obtained under some scenarios when the proportion of missing data is not too large. The proposed methodology is also applied to the randomized evaluation of the Mexican universal health insurance program. An open-source software package is available for implementing the proposed research. [ABSTRACT FROM AUTHOR]

AbstractData-driven decision making plays an important role even in high stakes settings like medicine and public policy. Learning optimal policies from observed data requires a careful formulation of the utility function whose expected value is maximized across a population. Although researchers typically use utilities that depend on observed outcomes alone, in many settings the decision maker’s utility function is more properly characterized by the joint set of potential outcomes under all actions. For example, the Hippocratic principle to “do no harm” implies that the cost of causing death to a patient who would otherwise survive without treatment is greater than the cost of forgoing life-saving treatment. We consider optimal policy learning with asymmetric counterfactual utility functions of this form that consider the joint set of potential outcomes. We show that asymmetric counterfactual utilities lead to an unidentifiable expected utility function, and so we first partially identify it. Drawing on statistical decision theory, we then derive minimax decision rules by minimizing the maximum expected utility loss relative to different alternative policies. We show that one can learn minimax loss decision rules from observed data by solving intermediate classification problems, and establish that the finite sample excess expected utility loss of this procedure is bounded by the regret of these intermediate classifiers. We apply this conceptual framework and methodology to the decision about whether or not to use right heart catheterization for patients with possible pulmonary hypertension. Supplementary materials for this article are available online. [ABSTRACT FROM AUTHOR]

In this paper, a delayed predator-prey model is considered. The existence and stability of the positive equilibrium are investigated by choosing the delay as a bifurcation parameter. We see that Hopf bifurcation can occur as crosses some critical values. The direction of the Hopf bifurcations and the stability of the bifurcation periodic solutions are also determined by using the center manifold and normal form theory. Furthermore, based on the global Hopf bifurcation theorem for general function differential equations, which was established by J. Wu using fixed point theorem and degree theory methods, the existence of global Hopf bifurcation is investigated. Finally, numerical simulations to support the analytical conclusions are carried out. [ABSTRACT FROM AUTHOR]

A novel diacetylene–containing main chain-type polymer, poly[2,6-bis(4-propargyl-oxy-benzoyl)pyridine] (P1), was synthesized via oxidative coupling reaction with a new propargyl-terminated monomer, 2,6-bis(4-propargyl-oxy-benzoyl)pyridine (M1), which was incorporated a substituted pyridine into the molecular chain of model monomer, 4,4′-bis(propargyl-oxy)benzophenone (M0). The structures of the new monomer and the resulting polymer were verified by Fourier transform infrared and proton nuclear magnetic resonance spectroscopies. Differential scanning calorimetry was used to investigate the curing behaviors of M1 and P1. The onset curing temperature of M1 was 199.0°C, and the exothermic enthalpy of M1 was 973.4 J g−1, while the initial curing temperature for polymer P1 reduced by 48°C and the exothermic enthalpy was almost half. Thermogravimetric analysis (TGA) showed the excellent thermal stabilities of M1 and its polymer in argon atmosphere (the decomposition temperatures at 5% weight loss were 446°C for M1 and 370°C for P1 and their char yields at 800°C exceeded 71%). The above TGA data were superior to that of the model monomer (M0) and its polymer (P0) under the same conditions. [ABSTRACT FROM AUTHOR]

Models based on multivariate t distributions are widely applied to analyze data with heavy tails. However, all the marginal distributions of the multivariate t distributions are restricted to have the same degrees of freedom, making these models unable to describe different marginal heavy-tailedness. We generalize the traditional multivariate t distributions to non-elliptically contoured multivariate t distributions, allowing for different marginal degrees of freedom. We apply the non-elliptically contoured multivariate t distributions to three widely-used models: the Heckman selection model with different degrees of freedom for selection and outcome equations, the multivariate Robit model with different degrees of freedom for marginal responses, and the linear mixed-effects model with different degrees of freedom for random effects and within-subject errors. Based on the normal mixture representation of our t distribution, we propose efficient Bayesian inferential procedures for the model parameters based on data augmentation and parameter expansion. We show via simulation studies and real data examples that the conclusions are sensitive to the existence of different marginal heavy-tailedness. [ABSTRACT FROM AUTHOR]

In this paper, the effect of delay on a nonlinear chaotic chemostat system with delayed feedback is investigated by regarding delay as a parameter. At first, the stability of the positive equilibrium and the existence of Hopf bifurcations are obtained. Then an explicit algorithm for determining the direction and the stability of the bifurcating periodic solutions is derived by using the normal form theory and center manifold argument. Finally, some numerical simulation examples are given, which indicate that the chaotic oscillation can be converted into a stable steady state or a stable periodic orbit when delay passes through certain critical values. [ABSTRACT FROM AUTHOR]

In this paper, a SIR model with two delays and general nonlinear incidence rate is considered. The local and global asymptotical stabilities of the disease-free equilibrium are given. The local asymptotical stability and the existence of Hopf bifurcations at the endemic equilibrium are also established by analyzing the distribution of the characteristic values. Furthermore, the sufficient conditions for the permanence of the system are given. Some numerical simulations to support the analytical conclusions are carried out. At last, some conclusions are given. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

This work presents two methods, the Least-square and Bayesian method, to solve the multiple mapping problem in extracting gene expression profiles through the next-generation sequencing. We parallel the tag sequences to genome, and partition them to improving the methods' efficiency. The essential feature of these methods is that they can solve the multiple mapping problem between genes and short-reads, while generating almost the same estimation in single-mapping situation as the traditional approaches. These two methods are compared by simulation and a real example, which was generated from radiation-induced lung cancer cells (A549), through mapping short-reads to human ncRNA database. The results show that the Bayesian method, as realized by Gibbs sampler, is more efficient and robust than the Least-square method. [ABSTRACT FROM AUTHOR]

Objective: To explore the appropriate treatment strategies, clinical outcomes, and prognostic factors of patients with pulmonary‐limited metastases derived from colorectal cancer (CRC), usually manifested as a less aggressive course. Methods: A retrospective review was conducted in 331 CRC patients diagnosed with pulmonary‐limited metastases at a single institution between January 2011 and November 2017. The Kaplan–Meier method was used to calculate the overall survival (OS). Further analysis was conducted according to treatment modalities. Univariate and multivariate analyses were used to determine potential prognostic factors influencing OS. Results: With a median follow‐up time of 38.6 months, the median OS in all patients was 45.2 months. A total of 163 patients received intensive local treatment with a median OS of 76.4 months, whereas 168 patients received palliative systemic treatment with a median OS of 29.7 months. The median OS was 68.9 months for patients treated with radiotherapy/radiofrequency ablation, with similar efficacy compared to surgery group, whose OS had not reached yet. No survival benefits were observed from the additional targeted therapy in systemic treatment group. The prognostic analysis demonstrated unilateral/bilateral lesions, synchronous/metachronous metastases, intensive local treatment, and resection of primary lesion that were significantly associated with survival of patients. Conclusions: Intensive local treatment alone for pulmonary lesions was associated with excellent survival in certain patients with CRC presented with metastases confined to lungs. Doublet systemic chemotherapy as the first‐line treatment also revealed satisfied efficacy and safety. [ABSTRACT FROM AUTHOR]

The article discusses the mis-classifications and errors in measurement in the study of effect of exposures. The article highlights the problem of exposure in the context of multiplicative interaction and additive interaction. The concept has been analysed with the help of mathematical equations. Topics discussed include bias, naive estimator and use of risk differences.

Objective: To construct and validate a prediction model based on dual-layer detector spectral CT (DLCT) and clinico-radiologic features to predict the microsatellite instability (MSI) status of gastric cancer (GC) and to explore the relationship between the prediction results and patient prognosis. Methods: A total of 264 GC patients who underwent preoperative DLCT examination were randomly allocated into the training set (n = 187) and validation set (n = 80). Clinico-radiologic features and DLCT parameters were used to build the clinical and DLCT model through multivariate logistic regression analysis. A combined DLCT parameter (CDLCT) was constructed to predict MSI. A combined prediction model was constructed using multivariate logistic regression analysis by integrating the significant clinico-radiologic features and CDLCT. The Kaplan–Meier survival analysis was used to explore the prognostic significant of the prediction results of the combined model. Results: In this study, there were 70 (26.52%) MSI-high (MSI-H) GC patients. Tumor location and CT_N staging were independent risk factors for MSI-H. In the validation set, the area under the curve (AUC) of the clinical model and DLCT model for predicting MSI status was 0.721 and 0.837, respectively. The combined model achieved a high prediction efficacy in the validation set, with AUC, sensitivity, and specificity of 0.879, 78.95%, and 75.4%, respectively. Survival analysis demonstrated that the combined model could stratify GC patients according to recurrence-free survival (p = 0.010). Conclusion: The combined model provides an efficient tool for predicting the MSI status of GC noninvasively and tumor recurrence risk stratification after surgery. Critical relevance statement: MSI is an important molecular subtype in gastric cancer (GC). But MSI can only be evaluated using biopsy or postoperative tumor tissues. Our study developed a combined model based on DLCT which could effectively predict MSI preoperatively. Our result also showed that the combined model could stratify patients according to recurrence-free survival. It may be valuable for clinicians in choosing appropriate treatment strategies to avoid tumor recurrence and predicting clinical prognosis in GC. Key points: • Tumor location and CT_N staging were independent predictors for MSI-H in GC. • Quantitative DLCT parameters showed potential in predicting MSI status in GC. • The combined model integrating clinico-radiologic features and CDLCT could improve the predictive performance. • The prediction results could stratify the risk of tumor recurrence after surgery. [ABSTRACT FROM AUTHOR]

In this paper, a model with time delay describing biodegradation of Microcystins (MCs) is investigated. Firstly, the stability of the positive equilibrium and the existence of Hopf bifurcations are obtained. Furthermore, an explicit algorithm for determining the direction and the stability of the bifurcating periodic solutions is derived by using the normal form theory and center manifold argument. Finally, some numerical simulations are carried out to illustrate the applications of the results. [ABSTRACT FROM AUTHOR]

• A polygonal hysteretic model for FRP-retrofitted corroded RC columns was developed. • The parameters of the developed hysteretic model were identified based on test data. • Empirical prediction equations were generated for the parameters of the developed hysteretic model. • The developed hysteretic model was validated and applied for seismic collapse analysis. A hysteresis model was developed for fiber reinforced polymer (FRP)-retrofitted reinforced concrete (RC) columns with corroded reinforcing bars. The test data of 49 FRP-retrofitted corroded columns and 19 intact columns (with no corrosion or FRP wraps) under repeat-cyclic loading were collected to establish a database. A polygonal model was adopted to simulate the hysteretic behavior of FRP-retrofitted corroded columns. This was determined using backbone and cyclic parameters. For the backbone parameters, a hybrid influence factor (HIF) was introduced to incorporate the coupling effects of corrosion and FRP retrofitting. A suite of empirical equations was developed using multivariate linear regression analysis to predict the HIFs of each backbone parameter in association with the corrosion rate and important column design parameters. Moreover, an empirical relationship was developed to determine the cyclic parameters of the hysteretic model using a regression analysis. The predicted hysteretic curves were compared with the experimental results, demonstrating sufficient accuracy for both intra- and extra-database tests. Finally, the developed hysteretic model was used to establish a macro-type structural model for the FRP-retrofitted corroded RC frames. This benefitted the analysis of structural collapse under earthquakes, and the effects of the corrosion rate and FRP retrofitting schemes on the seismic collapse capacity of RC frames were examined. [ABSTRACT FROM AUTHOR]

Purpose: Chemoradiotherapy (CRT) remains the standard treatment for locally advanced rectal cancer (LARC). This phase 2 clinical trial was designed to evaluate the efficacy and safety of neoadjuvant triplet chemotherapy with mFOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin, and irinotecan) in LARC. Patients and methods: The patients with LARC (the lower edge more than 5 cm from the anal verge) received up to 5 cycles of mFOLFOXIRI. MRI was performed to assess the baseline and postchemotherapy TN stage. Radical resection was performed within 4–6 weeks from the last dose of chemotherapy if the tumor shrank or remained stable. Adjuvant chemotherapy with mFOLFOX6 or XELOX was recommended. Postoperative radiation was planned for R1 resection, ypT4b, ypN2 and a positive CRM. The primary endpoint was the pathological complete response (pCR) rate. Results: From February 2016 to March 2019, 50 patients were enrolled. Forty-eight (96%) were clinically node-positive, 28 (56.5%) with MRF invasion and 39 (78.4%) were EMVI positive. The median cycle of neoadjuvant mFOLFOXIRI chemotherapy was 5 (range,1–5). A total of 46/50 (92%) patients underwent total mesorectal excision (TME) surgery, all with R0 resection. The pCR rate was 4.3% (2/46). Twenty-three of 46 (50%) patients with cN + achieved a pathological node-negative status. The proportions of pathologically positive CRM and EMVI were 2.2% and 34.7%, respectively. Adjuvant radiotherapy was given to 14/46 (30.4%) patients. The most common Grade 3 or > toxicities included neutrocytopenia (50%), leukopenia (14%) and diarrhea (12%) during the neoadjuvant chemotherapy period. Clinically meaningful postoperative complications included pneumonia (n = 1), pelvic infection (n = 1) and anastomotic fistula (n = 1). With a median follow-up time of 51.2 months, local recurrences and distant metastases were confirmed in 3 (6.5%) and 9 (19.6%) of cases, respectively. The 3-year disease free survival (DFS) and overall survival (OS)rates were 75.8% and 86.8%. Conclusion: Neoadjuvant chemotherapy with mFOLFOXIRI yielded a significant down-staging effect and seemed to be effective in eliminating EMVI and transforming the positive MRF to negative in LARC. The survival results are promising. The long-term follow-up showed promising DFS and OS rates accompanied by a favorable safety profile. Trial registration: ClinicalTrials.gov identifier: NCT03443661, 23/02/2018. [ABSTRACT FROM AUTHOR]

Metal smelting have brought severe metal(loid)s contamination to the soil. Spatial distribution and pollution source analysis for soil metal(loid)s in an abandoned lead/zinc smelter were studied. The results showed that soil was contaminated heavily with metal(loid)s. The mean of lead (Pb), arsenic (As), cadmium (Cd), mercury (Hg) and antimony (Sb) content in topsoil is 9.7, 8.2, 5.0, 2.3, and 1.2 times higher than the risk screening value for soil contamination of development land of China (GB36600-2018), respectively. Cd is mainly enriched in the 0–6 m depth of site soil while As and Pb mainly deposited in the 0–4 m layer. The spatial distribution of soil metal(loid)s is significantly correlated with the pollution source in the different functional areas of smelter. As, Hg, Sb, Pb and copper (Cu) were mainly distributed in pyrometallurgical area, while Cd, thallium (Tl) and zinc (Zn) was mainly existed in both hydrometallurgical area and raw material storage area. Soil metal(loid)s pollution sources in the abandoned smelter are mainly contributed to the anthropogenic sources, accounting for 84.5%. Specifically, Pb, Tl, As, Hg, Sb and Cu mainly from atmospheric deposition (55.9%), Cd and Zn mainly from surface runoff (28.6%), While nickel (Ni) mainly comes from parent material (15.5%). The results clarified the spatial distribution and their sources in different functional areas of the smelter, providing a new thought for the risk prevention and control of metal(loid)s in polluted site soil. [Display omitted] [ABSTRACT FROM AUTHOR]

Although caring and raising children is the duty of all parents, some animals relieve themselves of this labored work by relying on others to raise their young. After the host has made a nest and laid eggs, the parasite locates the nest and lays a few eggs in the host’s nest. Several possible interactions occur between the host and parasite in brood parasitism: the parasite does not destroy the host’s eggs and the host does not abandon her nest with eggs. Here, we establish a mathematical framework for studying an ecological model on brood parasitism with stage structure of the parasite, where time delay represents the incubation period of the parasite. For the proposed model, we studied the impact of incubation time delay on the coexistence equilibrium. By using corresponding characteristic equations, the local stability behavior of each of the feasible equilibria of the model and existence of Hopf bifurcations at the coexistence equilibrium are established. Further, the global properties of some equilibria are established using Lyapunov–LaSalle invariance principle. The incubation time delay was found to be crucial for establishing stability behavior. When the incubation time delay increased and crossed some critical values, Hopf bifurcation may occur at the coexistence equilibrium. Further, by using normal form and center manifold theories, formulas were established to determine the stability and direction of the Hopf bifurcation. Numerical simulations were conducted to support the theoretical analysis. Our mathematical model could help lay a foundation for further studies on brood parasitism by the cuckoo bird. [ABSTRACT FROM AUTHOR]

We investigate the dynamical behavior of a delayed HIV infection model with general incidence rate and immune impairment. We derive two threshold parameters, the basic reproduction number R0 and the immune response reproduction number R1. By using Lyapunov functional and LaSalle invariance principle, we prove the global stability of the infection-free equilibrium and the infected equilibrium without immunity. Furthermore, the existence of Hopf bifurcations at the infected equilibrium with CTL response is also studied. By theoretical analysis and numerical simulations, the effect of the immune impairment rate on the stability of the infected equilibrium with CTL response has been studied. [ABSTRACT FROM AUTHOR]

This paper investigates the dynamics of an HTLV-I infection model with intracellular delay and immune activation delay. The primary objective of the study is to consider the effect of the time delay on the stability of the infected equilibrium. Two sharp threshold parameters $\Re_{0}$ and $\Re_{1}$ are identified as the basic reproduction number for viral infection and for CTLs response, respectively, which determine the long time behaviors of the viral infection. In particular, our mathematical analysis reveals that a Hopf bifurcation occurs when immune activation delay passes through a critical value. Using the normal form theory and center manifold arguments, the explicit formulae which determine the stability, the direction, and the period of bifurcating periodic solutions are derived. Numerical simulations are given to support the theoretical results. [ABSTRACT FROM AUTHOR]

In this paper, a delayed virus model with two different transmission methods and treatments is investigated. This model is a time-delayed version of the model in (Zhang et al. in Comput. Math. Methods Med. 2015:758362, 2015). We show that the virus-free equilibrium is locally asymptotically stable if the basic reproduction number is smaller than one, and by regarding the time delay as a bifurcation parameter, the existence of local Hopf bifurcation is investigated. The results show that time delay can change the stability of the endemic equilibrium. Finally, we give some numerical simulations to illustrate the theoretical findings. [ABSTRACT FROM AUTHOR]

Purpose: We conducted a single-arm prospective phase II study to determine the efficacy and safety of the first-line treatment of advanced pancreatic cancer with nab-paclitaxel and S-1 followed by S-1 maintenance therapy.Methods: Nab-paclitaxel was administered intravenously on days 1 and 8 at 120 mg/m2. S-1 at 120 mg/day (for surface area ≥ 1.5 m2), 100 mg/day (for surface area between 1.25-1.5 m2), and 80 mg/day (for surface area < 1.25 m2) were given two times daily on days 1-14 every 3 weeks. Patients who achieved response and stable disease after 6 cycles were given S-1 maintenance treatment in the same schedule until disease progression or unacceptable toxicity developed. The primary endpoint was objective response rate (ORR), and the secondary endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety. Between 01/2015 and 07/2017, 32 patients were enrolled.Results: The ORR in the intention-to-treat (ITT) population (N = 32) was 53.1%, and the DCR was 87.5%. In the 30 evaluable patients, the ORR and DCR were 56.7 and 93.3%, respectively. The median follow-up time was 18 (range 12-36) months, the median PFS was 6.2 (range 4.4-8) months, and the median OS was 13.6 (range 8.7-18.5) months. The incidence of grade 3/4 neutropenia was 27.6%. Other grade 3 adverse events included 1 (3.1%) hand-foot syndrome, 1 (3.1%) rash and 2 (6.3%) diarrheas.Conclusions: Nab-paclitaxel and S-1 regimen has presented encouraging ORR, OS, and manageable toxicities as first-line therapy for advanced pancreatic cancer. [ABSTRACT FROM AUTHOR]

Dermatologic toxicities resulting in dose reduction or discontinuation of treatment pose challenges for targeted anticancer therapies. We conducted this randomized, double-blind, placebo-controlled trial to investigate the efficacy of topical application of Compound Danxiong Granules (CDG) for treatment of dermatologic toxicities associated with targeted anticancer therapies. One hundred and ten patients with dermatologic toxicities induced by targeted anticancer therapies were randomly assigned to CDG or placebo group. Each crude herb (Rhizoma Chuanxiong, Paeonia suffruticosa Andr., Cortex Phellodendri, Geranium sibiricum L., and Flos Carthami) was prepared as an instant herbal powder. Application of the CDG via topical washes lasted 20 minutes, twice daily, for 10 days. The primary outcome was the total effective rate, defined as reduction in at least one grade of skin toxicity. The total effective rate was 77.61% (52/67) in the CDG group and 27.27% (9/33) in the placebo group (P<0.0001). Compared to the placebo treatment, CDG treatment achieved a higher total effective rate for hand-foot skin reaction (95.45% versus 27.27%), acneiform eruption (69.23% versus 30.78%), and paronychia (68.42% versus 22.22%). Topical application of CDG can effectively attenuate dermatologic toxicities induced by targeted anticancer therapies. The effect of CDG was more pronounced in hand-foot skin reaction. [ABSTRACT FROM AUTHOR]