Time-dependent Analysis Research Articles

Synthesis, crystal structure, cytotoxicity, in-detail experimental and computational CT-DNA interaction studies of 2-picolinate Pd(II) and Pt(II) complexes

A new Pd(II) complex of formula [Pd(en)(2-pyc)]+ (where, en is ethylenediamine and 2-pyc is 2-pyridinecarboxylate anion) and its reported Pt(II) analogue, i.e. [Pt(en)(2-pyc)]+ have been made by an improved synthetic procedure, yielding above 80%. They have been characterized by FT-IR, UV-Vis, 1H NMR, 13C NMR, conductivity and elemental analysis. Single crystal structural determination of [Pt(en)(2-pyc)]+ displayed that the Pt(II) cation in this complex coordinated by 2-pyc and en each as five member chelate resulting in slightly distorted square-planar array. The time-dependent spectroscopic analysis of these compounds in aqueous medium demonstrated their structural stabilities. The cytotoxic activities of Pd(II) and Pt(II) complexes, free 2-pyc and carboplatin (as standard drug) were assayed in-vitro against the HCT-116 and MCF-7 as cancerous and MCF 10 A and CCD-841 as normal cell lines. They showed the IC50 order of: carboplatin > 2-pyc > Pt(II) > Pd(II) and lower activities against non-cancerous cells. CT-DNA binding of the Pd(II), Pt(II) and 2-pyc free ligand were explored individually. In this relation, UV-Vis and fluorescence titrations disclosed quenching of CT-DNA absorption and emissions by the compounds via dynamic mechanism and formation of H-bonds and van der Waals forces between them. The interaction was further validated and verified by viscosity measurements and gel electrophoresis. Partition coefficient determination showed that all three compounds have more lipophilicity than cisplatin. Furthermore, docking analysis and molecular dynamics simulation were done to evaluate the nature of interaction between aforementioned compounds and CT-DNA. The finding results demonstrated that these agents interact with CT-DNA via groove binding and were in agreement with experimental results. Communicated by Ramaswamy H. Sarma

Reliability analysis of time-dependent problems based on ensemble learning of surrogate models

PurposeSurrogate models are extensively used to substitute real models which are expensive to evaluate in the time-dependent reliability analysis. Normally, different surrogate models have different scopes of application. However, information is often insufficient for analysts to select the most appropriate surrogate model for a specific application. Thus, the result precited by individual surrogate model tends to be suboptimal or even inaccurate. Ensemble model can effectively deal with the above concern. This work aims to study the application of ensemble model for reliability analysis of time-independent problems.Design/methodology/approachIn this work, a method of reliability analysis for time-dependent problems based on ensemble learning of surrogate models is developed. The ensemble of surrogate models includes Kriging, radial basis function, and support vector machine. The prediction is approximated by the weighted average model. The ensemble learning of surrogate models is updated by finding and adding the sample points with large prediction errors throughout the entire procedure.FindingsThe effectiveness of the proposed method is verified by several examples. The results show that the ensemble of surrogate models can effectively propagate the uncertainty of time-varying problems, and evaluate the reliability with high prediction accuracy and computational efficiency.Originality/valueThis work proposes an adaptive learning framework for the uncertainty propagation of time-dependent problems based on the ensemble of surrogate models. Compared with individual surrogate models, the ensemble model not only saves the effort of selecting an appropriate surrogate model especially when the knowledge of unknown problem is lacking, but also improves the prediction accuracy and computational efficiency.

A double-loop Kriging model algorithm combined with importance sampling for time-dependent reliability analysis

A double-loop Kriging model algorithm combined with importance sampling for time-dependent reliability analysis

Impact of minimally invasive total mesoesophageal excision and minimally invasive esophagectomy on failure patterns of locally advanced esophageal squamous cell carcinoma: a matched cohort study with long-term follow-up.

The effects of minimally invasive total mesoesophageal excision (MITME) on the long-term prognosis of locally advanced esophageal squamous cell carcinoma (ESCC) remain unknown. The objective of this study was to compare the static and dynamic failure patterns of MITME and minimally invasive esophagectomy (MIE) for locally advanced ESCC. We use propensity score matching (PSM) method to analyze the postoperative failure patterns of the two groups. Cumulative event curves were analyzed for cumulative incidence of failure between different groups, and independent prognostic factors were assessed using time-dependent multivariate analyses. The risk of dynamic failure calculated at 12-month intervals was compared between the two groups using the lifetime table. A total of 366 ESCC patients were studied by 1:1 PSM for T stage and TNM stage (MITME group, n = 183; MIE group, n = 183). In the matched cohort, there was significant differences between the MITME and MIE groups in the failure pattern of regional lymph node recurrence (0.5 vs 3.8%, P = 0.032) and non-tumor death (10.9 vs 31.7%, P < 0.001). The cumulative event curve found that the 5-year cumulative failure rate was lower in the MITME group than in the MIE group (3.3 vs 17.1%, P = 0.026) after 5years of survival. In addition, multivariate Cox regression analysis showed that MIE was an independent poor prognostic factor for a high cumulative failure rate in locally advanced ESCC patients at 5years after surgery (HR:4.110; 95% CI 1.047-16.135; P = 0.043). The dynamic risk curve showed that the MITME group had a lower risk of failure within 5years after surgery than the MIE group. Considering that MITME can significantly improve the postoperative failure pattern and the benefit lasts for at least 5years, it is feasible to use MITME as a treatment for locally advanced ESCC.

Time-Dependent Reliability Analysis of RC Bridges Considering Shrinkage, Creep, Resistance Degradation, and Vehicle Load Flows

Due to concrete shrinkage, concrete creep, resistance degradation, and vehicle load flows, the long-term performance of reinforced concrete bridges exhibits time-varying characteristics. The vehicle-borne process is a nonstationary random process, which interacts with concrete shrinkage, concrete creep, and resistance degradation to cause constant changes in bridge internal force and deformation, further, bridge dynamic reliability occurs. This study presented a reasonable method for calculating the time-varying reliability of simply supported girder bridges under the effects of traffic loads and shrinkage creep. Stochastic truck-load models were simulated based on site-specific weigh-in-motion measurements, then the internal forces of the bridge were calculated when the mean value of vehicle-mounted effects increases by 1% per year. Considering the resistance degradation and load effect increase, the reliability of the RC bridge in serviceability limit state and capacity-carrying ultimate state were analyzed using first-passage probability method and Monte Carlo method, respectively. The accuracy of the proposed method was verified by comparison. The evaluation results show that the failure probability including shrinkage and creep has increased significantly; creep is affected by the bridge span and the number of main girders, and the reliability assessment results are safer for bridges with smaller spans.

Time-Dependent Reliability Analysis of Fracture Failure of Corroded Cast Iron Water Pipes and Bayesian Updating for Lifetime Prediction

Affected by the underground soil environment, buried cast iron pipelines are subject to corrosion during their long-term service, resulting in damage accumulation to the pipe wall and the eventual fracture failure of pipes. This paper aims to propose a probabilistic method to quantitively assess the time-dependent reliability of fracture failure of corroded cast iron pipes. A Gamma-based corrosion process of the pipe wall is derived according to the reported corrosion models. The first-order reliability method and the Monte Carlo simulation are used to cross-validate and conduct the time-dependent reliability analysis based on the fracture failure criterion. Furthermore, uncertain physical parameters of the pipes are updated by the Bayesian Markov Chain Monte Carlo (MCMC) algorithm based on the regional historical data of failed pipes, and lifetime predictions of buried cast iron pipelines are then obtained. A worked example is provided to illustrate the application of the proposed method. It is found that the Gamma process can well simulate the corrosion process hence can be employed to calculate the probability of pipe fracture failure. Sensitivity analysis reveals that the pipe internal water pressure, the fracture toughness, and the geometry of corrosion pits are the most influential parameters to the probability of fracture failure. It is also found that the predicted lifetime of corroded cast iron pipes in the worked example decreases from 110 to 85 years after the Bayesian updating.

High-efficient CO2-to-protein bioconversion by oleaginous Coccomyxa subellipsoidea using light quality shift and nitrogen supplementation strategy

Oleaginous microalgae are usually used in CO2-to-lipid bioprocess for biofuels production but still faced the low productivity of biomass and lipid with uncompetitive cost. A novel CO2-to-protein bioconversion pattern by oleaginous Coccomyxa subellipsoidea was implemented in the present work as high-value application of CO2. Results demonstrated that the highest CO2 fixation rate (RCO2, 0.74 g/L/d) and protein productivity (178 mg/L/d) with lower protein content (42.33% DW) were achieved under red light; but under blue light, the highest protein content (52.07% DW) were reached with lower productivity (156.94 mg/L/d) and RCO2 (0.52 g/L/d). The analysis of key genes transcription and enzymes activity revealed that red light boosted the photosynthetic activity and photoprotection contributing to the high-efficient CO2 fixation. Based on this, a tailored light quality shift and nitrogen supplementation in a two-phase culture (red light in phase 1; red: blue-1:1 with nitrate addition in phase 2) was developed, reaching the maximal biomass yield (6.12 g/L), RCO2 (0.90 g/L/d), protein content (52.00% DW) with protein productivity (265.83 mg/L/d) simultaneously, 2.0-fold, 1.2-fold, 2.9-fold and 2.3-fold higher than that under white light as the control. The highest contents of AAs (47.12% DW) and EAAs (18.67% DW) with essential amino acid index (1.3) were achieved, superior to FAO/WHO reference. Time-dependent gene transcription analysis revealed the up-regulated photosynthesis and nitrogen assimilation in the two-phase culture. This work demonstrated that the oleaginous C. subellipsoidea could be well used for protein production and CO2 fixation, providing a promising application approach in carbon neutrality and high-yield protein production.

Zymosan A produces a rapid and sustained antidepressant effect in chronically stressed mice by stimulating hippocampal microglia.

Recent studies had reported that compounds that stimulate microglia could be developed as potential drugs for the treatment of depression due to their reversal effect on depression-like behaviors in chronically stressed mice. Zymosan A is a cell wall preparation of Saccharomyces cerevisiae composed of β-glucans. Based on its immuno-stimulatory activities, we hypothesized that zymosan A might have a therapeutic effect on depression. Our results showed that a single injection of zymosan A 5 h before behavioral tests at a dose of 1 or 2 mg/kg, but not at a dose of 0.5 mg/kg, reversed chronic unpredictable stress (CUS)-induced depression-like behaviors in mice in the tail suspension test, forced swimming test, and sucrose preference test. Time-dependent analysis showed that the antidepressant effect of zymosan A (2 mg/kg) in CUS mice became statistically significant at 5 and 8 h, but not at 3 h, and persisted for at least 7 days. Fourteen days after a single injection of zymosan A, no antidepressant effect was observed anymore. However, the disappeared antidepressant effect of zymosan A was restored by a second zymosan A injection (2 mg/kg, 5 h) 14 days after the first zymosan A injection. Stimulation of microglia was essential for the antidepressant effect of zymosan A because pre-inhibition of microglia by minocycline or pre-depletion of microglia by PLX3397 prevented the antidepressant effect of zymosan A. Based on these effects of zymosan A, zymosan A administration could be developed as a new strategy for the treatment of depression.

Time-dependent system reliability analysis using adaptive single-loop Kriging with probability of rejecting classification

Time-dependent system reliability analysis using adaptive single-loop Kriging with probability of rejecting classification

Time-Dependent Reliability Analysis for Deflection of a Reinforced Concrete Box Girder Bridge

Prior to casting of concrete, proper supervision and attention to camber provision in bridge construction are required. It is also critical to use an appropriate quality control manual, pay due attention to reinforcement bar placement, and have a high level of formwork design before construction begins. If these issues are not properly addressed, performance of structures will be affected. In this research, performance of a 40.5m box-girder reinforced concrete bridge which was constructed without having proper camber is studied. As camber was the most important issue of the bridge under investigation, the impact on strength and serviceability requirements is compared to the standard. A dynamic load test with an Arduino type accelerometer is performed to assess the bridge's current condition in relation to the serviceability limit requirement. The deterioration of reinforced concrete (RC) sections due to reinforcement corrosion, creep, and an increase in load intensity, as well as the corresponding statistical distributions are considered to estimate the long-term effect of bridge deflection. The time-variant analysis results show that a linear decrease in deflection reliability indices with the bridge's expected service life of 58 years and strengthening it increased to 85 years.

Macrophage-derived exosomes promote intestinal mucosal barrier dysfunction in inflammatory bowel disease by regulating TMIGD1 via mircroRNA-223.

Exosomes are effective mediators of cell-to-cell interactions and transport several regulatory molecules, including microRNAs (miRNAs), involved in diverse fundamental biological processes. The role of macrophage-derived exosomes in the development of inflammatory bowel disease (IBD) has not been previously reported. This study investigated specific miRNAs in macrophage-derived exosomes in IBD and their molecular mechanism. A dextran sulfate sodium (DSS)-induced IBD mouse model was established. The culture supernatant of murine bone marrow-derived macrophages (BMDMs) cultured with or without lipopolysaccharide (LPS) was used for isolating exosomes, which were subjected to miRNA sequencing. Lentiviruses were used to alter miRNA expression and investigate the role of macrophage-derived exosomal miRNAs. Both mouse and human organoids were co-cultured with macrophages in a Transwell system to model cellular IBD in vitro. LPS-induced macrophages released exosomes containing various miRNAs and exacerbated IBD. Based on miRNA sequencing of macrophage-derived exosomes, miR-223 was selected for further analysis. Exosomes with upregulated miR-223 expression contributed to the exacerbation of intestinal barrier dysfunction in vivo, which was further verified using both mouse and human colon organoids. Furthermore, time-dependent analysis of the mRNAs in DSS-induced colitis mouse tissue and miR-223 target gene prediction were performed to select the candidate gene, resulting in the identification of the barrier-related factor Tmigd1. Macrophage-derived exosomal miR-223 has a novel role in the progression of DSS-induced colitis by inducing intestinal barrier dysfunction through the inhibition of TMIGD1.

Cleaner production of energy and fuels from a renewable energy-based self-sufficient system with energy storage options

The present study investigates a newly developed solar and wind-driven integrated energy system to achieve self-sufficiency for communities in a sustainable fashion. In order to overcome the fluctuating nature of solar and wind sources, energy storage options are considered through reliable meteorological data and capacities. The non-thermal electricity, heat, and cooling demands of a community with 65,000 people are met by using a 340 MW wind farm and 1500 MWp linear Fresnel concentrated solar system coupled with thermal energy storage. The integrated system consists of a wind farm with 170 wind turbines, linear Fresnel concentrated solar plant, molten salt energy storage tanks, steam Rankine cycle, lithium-bromide absorption refrigeration cycle, anion exchange membrane electrolysis unit, multi-effect distillation desalination unit, district heating system. Both steady-state analysis for different operating conditions and time-dependent analysis with changing source and load data are carried out from energy and exergy aspects of thermodynamics. The proposed system was able to meet 100 % of 363,344.7 MWh of electricity, 544,468.2 MWh of heat, and 192,112.7 MWh of cooling loads in a year; moreover, it generated 24,142 kt of fresh water and 38,843 t of hydrogen in a year, in order to exploit the excess and waste energy. For the overall integrated system, the average energy and exergy efficiencies are found to be 37.69 % and 28.27 %, respectively. In order to benefit from the full potential of wind and solar-based systems in a combined, the current study provides a unique solution with energy storage option and generates multiple useful outputs for the targeted communities in a sustainable manner.

Assessing the usefulness of a newly proposed metabolic score for visceral fat in predicting future diabetes: results from the NAGALA cohort study.

Visceral adipose tissue assessment holds significant importance in diabetes prevention. This study aimed to explore the association between the newly proposed Metabolic Score for Visceral Fat (METS-VF) and diabetes risk and to further assess the predictive power of the baseline METS-VF for the occurrence of diabetes in different future periods. This longitudinal cohort study included 15,464 subjects who underwent health screenings. The METS-VF, calculated using the formula developed by Bello-Chavolla etal., served as a surrogate marker for visceral fat obesity. The primary outcome of interest was the occurrence of diabetes during the follow-up period. Established multivariate Cox regression models and restricted cubic spline (RCS) regression models to assess the association between METS-VF and diabetes risk and its shape. Receiver operating characteristic (ROC) curves were used to compare the predictive power of METS-VF with body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), and visceral adiposity index (VAI) for diabetes, and time-dependent ROC analysis was conducted to assess the predictive capability of METS-VF for the occurrence of diabetes in various future periods. During a maximum follow-up period of 13 years, with a mean of 6.13 years, we observed that the cumulative risk of developing diabetes increased with increasing METS-VF quintiles. Multivariable-adjusted Cox regression analysis showed that each unit increase in METS-VF would increase the risk of diabetes by 68% (HR 1.68, 95% CI 1.13, 2.50), and further RCS regression analysis revealed a possible non-linear association between METS-VF and diabetes risk (P for non-linearity=0.002). In addition, after comparison by ROC analysis, we found that METS-VF had significantly higher predictive power for diabetes than other general/visceral adiposity indicators, and in time-dependent ROC analysis, we further considered the time-dependence of diabetes status and METS-VF and found that METS-VF had the highest predictive value for predicting medium- and long-term (6-10 years) diabetes risk. METS-VF, a novel indicator for assessing visceral adiposity, showed a significantly positive correlation with diabetes risk. It proved to be a superior risk marker in predicting the future onset of diabetes compared to other general/visceral adiposity indicators, particularly in forecasting medium- and long-term diabetes risk.

Quantitative characterization of archaeological bronzes based on thermal and compositional analysis

AbstractPulsed thermography has been applied to the quantitative characterization of the insertions of two ancient bronzes, the Boxer at Rest and the Hellenistic Prince. The analysis of the thermographic signal time dependence performed by a specifically developed model enabled the evaluation of the insertions’ thickness and of elements which could provide indications about the procedure followed for their insertion. This could be achieved by exploiting a semi‐empirical relation establishing the thermal diffusivity dependence on the total effective weighted concentration of Sn and Pb atoms obtained from the analysis of the values determined on samples containing different concentrations of Sn and Pb.

Surrogate-Based Time-Dependent Reliability Analysis for a Digital Twin

Abstract A mature digital twin (DT) is supposed to enable engineers to accurately evaluate the real-time reliability of a complex engineering system. However, in practical engineering problems, reliability analysis (RA) often involves nonlinear, implicit, and computationally expensive relationships between the performance and uncertain parameters, which makes it very challenging to conduct time-dependent reliability analysis (TRA) instantly and accurately for a DT. This article proposes a new surrogate-based time-dependent reliability analysis (STRA) method for a DT, specifically making the following three contributions: (i) the number of discrete time nodes used to convert the stochastic processes into a series of random variables in the expansion optimal linear estimation process is dynamically selected, leading to a good tradeoff between the accurate representation of stochastic processes and fast reliability evaluation; (ii) based on Voronoi partition sampling and a modified leave-one-out cross-validation procedure, multiple sensitive subdomains in each iteration are selected simultaneously to guide adaptive sampling at the insufficiently fitted vicinity of the limit state function, which helps accurately calculate the probability of failure and reduce the number of design-of-experiment (DoE) samples; and (iii) an improved weighted expected feasibility function is proposed considering the importance of each sample and the sensitivity of the subdomain to which it belongs, which further improves the sampling efficiency. The proposed STRA method is applied to the TRA of a numerical model, a corroded beam structure, and a cutterhead of a tunnel boring machine to demonstrate its effectiveness for realistic DT applications.

Haemodynamic forces predicting remodelling and outcome in patients with heart failure treated with sacubitril/valsartan.

A novel tool for the evaluation of left ventricular (LV) systo-diastolic function through echo-derived haemodynamic forces (HDFs) has been recently proposed. The present study aimed to assess the predictive value of HDFs on (i) 6month treatment response to sacubitril/valsartan in heart failure with reduced ejection fraction (HFrEF) patients and (ii) cardiovascular events. Eighty-nine consecutive HFrEF patients [70% males, 65±9years, LV ejection fraction (LVEF) 27±7%] initiating sacubitril/valsartan underwent clinical, laboratory, ultrasound and cardiopulmonary exercise testing evaluations. Patients experiencing no adverse events and showing ≥50% reduction in plasma N-terminal pro-B-type natriuretic peptide and/or ≥10% LVEF increase over 6months were considered responders. Patients were followed up for the composite endpoint of HF-related hospitalisation, atrial fibrillation and cardiovascular death. Forty-five (51%) patients were responders. Among baseline variables, only HDF-derived whole cardiac cycle LV strength (wLVS) was higher in responders (4.4±1.3 vs. 3.6±1.2; p=0.01). wLVS was also the only independent predictor of sacubitril/valsartan response at multivariable logistic regression analysis [odds ratio 1.36; 95% confidence interval (CI) 1.10-1.67], with good accuracy at receiver operating characteristic (ROC) analysis [optimal cutpoint: ≥3.7%; area under the curve (AUC)=0.736]. During a 33month (23-41) median follow-up, a wLVS increase after 6months (ΔwLVS) showed a high discrimination ability at time-dependent ROC analysis (optimal cut-off: ≥0.5%; AUC=0.811), stratified prognosis (log-rank p<0.0001) and remained an independent predictor for the composite endpoint (hazard ratio 0.76; 95% CI 0.61-0.95; p<0.01), after adjusting for clinical and instrumental variables. HDF analysis predicts sacubitril/valsartan response and might optimise decision-making in HFrEF patients.

Carotid Endarterectomy for Asymptomatic Stenosis Based on Duplex Ultrasound Alone Achieves Equivalent Perioperative and Long-Term Outcomes Relative to Advanced Imaging Based Endarterectomy

The purpose of this study is to compare both perioperative as well as long-term outcomes of patients undergoing carotid endarterectomy (CEA) for asymptomatic carotid bifurcation stenosis based on duplex ultrasound in isolation relative to a combination of duplex and more advanced imaging. All CEA in the VQI between January 2003 and May 2022 were queried. We identified 171,816 CEAs in the database. Exclusions were symptomatic carotid lesion (57,742), lack of imaging documentation (908), lack of advanced imaging status (1,816), simultaneous additional arterial intervention in the carotid, coronary, or peripheral arterial system (n=4,118), and anatomic high-risk status for CEA (n=4,071). Included patients were then placed into 1 of 2 cohorts: patients undergoing CEA based on duplex imaging alone (n=33,437) and those undergoing CEA based on advanced imaging (CTA, MRA, or invasive angiography) with or without duplex (n=69,715). We performed multivariable analysis for the following outcomes utilizing CEA based on duplex in isolation as 1 of the variables: perioperative neurological ischemic event utilizing binary logistic regression; combined 90-day mortality and neurological ischemic event utilizing binary logistic regression; neurological event in long-term follow-up with date of surgery serving as time zero; time dependent Cox regression analysis; mortality in long-term follow-up utilizing time-dependent Cox regression. Carotid endarterectomy based on duplex alone and CEA based on advanced imaging had essentially equivalent rates of 90-day mortality (0.9% vs. 1.0%, P=0.108); combined perioperative neurological event and 90-day mortality (2.0% vs. 2.2%, P=0.042); and, return to the operating room (1.6% vs. 1.7%, P=0.154). On multivariable analysis CEA based on advanced imaging was noted to have a slightly higher absolute rate of perioperative neurological event without achieving multivariable significance (1.3% vs. 1.2%, adjusted odds ratio 1.11 (0.98-1.25), P=0.092. CEA based on advanced imaging had a higher rate of neurological event after index hospital admission relative to duplex in isolation (hazard ratio (HR) 1.44 (1.31-1.60), P<0.001). However, the absolute percentage difference was just 0.5% (1.6% vs. 2.1%). CEA based on duplex alone was associated with a slightly increased risk of mortality in LTFU (HR 1.16 (1.11-1.21), P<0.001). At 5years the absolute risk of mortality was less than 1% different between the cohorts. Performing CEA for asymptomatic bifurcation stenosis based on duplex ultrasound alone is a safe practice which achieves clinically equivalent perioperative and long-term freedom from cerebral ischemia and mortality relative to CEA based on advanced imaging. This has potential implications for health care cost saving as well as avoidance of radiation and iodinated contrast.

Prognostic scoring system based on eosinophil- and basophil-related markers for predicting the prognosis of patients with stage II and stage III colorectal cancer: a retrospective cohort study.

Systemic inflammation is associated with the prognosis of colorectal cancer (CRC). The current study aimed to construct a comprehensively inflammatory prognostic scoring system named risk score (RS) based on eosinophil- and basophil-related markers and assess its prognostic value in patients with stage II and stage III CRC. A total of 3,986 patients were enrolled from January 2007 to December 2013. The last follow-up time was January 2019. They were randomly assigned to the training set and testing set in a 3:2 split ratio. Least absolute shrinkage and selection operator (LASSO)-Cox regression analysis was performed to select the optimal prognostic factors in the construction of RS. The Kaplan-Meier curve, time-dependent receiver operating characteristic (ROC), and Cox analysis were used to evaluate the association between RS and overall survival (OS). In the training set, all inflammatory markers showed certain prognostic values. Based on LASSO-Cox analysis, nine markers were integrated to construct RS. The Kaplan-Meier curve showed that a higher RS (RS > 0) had a significantly worse prognosis (log-rank p< 0.0001). RS (>0) remained an independent prognostic factor for OS (hazard ratio (HR): 1.70, 95% confidence interval (CI), 1.43-2.03, p< 0.001). The prognostic value of RS was validated in the entire cohort. Time-dependent ROC analysis showed that RS had a stable prognostic effect throughout the follow-up times and could enhance the prognostic ability of the stage by combination. Nomogram was established based on RS and clinicopathological factors for predicting OS in the training set and validated in the testing set. The area under the curve (AUC) values of the 3-year OS in the training and testing sets were 0.748 and 0.720, respectively. The nomogram had a satisfactory predictive accuracy and had better clinical application value than the tumor stage alone. RS might be an independent prognostic factor for OS in patients with stage II and III CRC, which is helpful for risk stratification of patients. Additionally, the nomogram might be used for personalized prediction and might contribute to formulating a better clinical treatment plan.

Time-dependent analysis of the impact on early cytomegalovirus reactivation of HLA mismatch and acute graft-versus-host disease after allogeneic hematopoietic cell transplantation from related donors in acquired aplastic anemia.

Cytomegalovirus (CMV) reactivation is an important issue in allogeneic hematopoietic cell transplantation (HCT). The incidence of early CMV reactivation is notably high in HLA-mismatched HCT. However, the interactions between HLA mismatch and acute graft-versus-host disease (aGvHD), a time-dependent event, make it methodologically challenging to evaluate the independent impact on CMV reactivation of the two variables. We retrospectively analyzed 355 patients with acquired aplastic anemia who received related donor transplants using a unified antithymocyte globulin-based platform. Patients were divided into group 1 (6/6 HLA match), group 2 (1-2/6 HLA allelic mismatch), and group 3 (3/6 HLA allelic mismatch). The impact of covariates was analyzed through two models: (1) time-dependent Cox and (2) dynamic landmarking analysis. The time-dependent Cox model showed that the HLA mismatch of 3/6 alleles (hazard ratio (HR) =1.852, P = .004) and aGvHD (HR = 1.009, P = .019) were independent risk factors for CMV reactivation. With the dynamic landmarking analysis, a higher HLA disparity correlated to increased early CMV reactivation (HR = 1.606, P = .001) at all time points. Developing aGvHD following HCT was generally associated with a higher incidence of CMV reactivation (HR = 1.623, P = .013), though its impact decreased with successive later landmark time points. In conclusion, our data suggest that the higher HLA disparity and aGvHD increases susceptibility to early CMV reactivation. In particular, the dynamic landmarking analysis demonstrated the time-varying effect of aGvHD on CMV reactivation, and HLA mismatch showed a profound impact over time following HCT.

SEER-based risk stratification system for patients with primary non-cirrhotic liver cancer

BackgroundLittle research has been done on the factors affecting the survival of patients with non-cirrhotic hepatocellular carcinoma (HCC-NCL). Our aim was to develop and validate a nomogram and a new risk stratification system that can evaluate overall survival (OS) in HCC-NCL patients.MethodsWe retrospectively analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2019 to study HCC-NCL patients. The patients were randomly split into training and validation groups at a 7:3 ratio and subjected to single-factor and multi-factor COX regression analysis. We then developed a nomogram and evaluated its accuracy and clinical validity using time-dependent ROC, DCA, and calibration curves. We compared the nomogram with the AJCC staging system by calculating C-index, NRI, and IDI. Finally, we used Kaplan–Meier curves to compare the nomogram and AJCC staging. These analyses were performed without altering the original intended meaning.ResultsAFP levels, surgical intervention, T-stage, tumor size, and M-stage were independent prognostic indicators for overall survival among the HCC-NCL population studied. We developed a nomogram based on these factors, and time-dependent ROC, calibration curves, DCA analyses, and C-index proved its accuracy. Compared to the AJCC staging system, the nomogram showed better prognostic accuracy through time-dependent ROC, DCA analyses, C-index, NRI, IDI, and Kaplan–Meier curves.ConclusionWe have developed and validated a survival nomogram applicable to HCC-NCL patients, with risk stratification. Our nomogram offers personalized treatment and management options superior to those provided by the AJCC staging system.