Storage time affects the level and diagnostic efficacy of plasma biomarkers for neurodegenerative diseases

Several promising plasma biomarker proteins,such as amyloid-β(Aβ),tau,neurofilament light chain,and glial fibrillary acidic protein,are widely used for the diagnosis of neurodegenerative diseases.However,little is known about the long-term stability of these biomarker proteins in plasma samples stored at-80°C.We aimed to explore how storage time would affect the diagnostic accuracy of these biomarkers using a large cohort.Plasma samples from 229 cognitively unimpaired individuals,encompassing healthy controls and those experiencing subjective cognitive decline,as well as 99 patients with cognitive impairment,comprising those with mild cognitive impairment and dementia,were acquired from the Sino Longitudinal Study on Cognitive Decline project.These samples were stored at-80°C for up to 6 years before being used in this study.Our results showed that plasma levels of Aβ42,Aβ40,neurofilament light chain,and glial fibrillary acidic protein were not significantly correlated with sample storage time.However,the level of total tau showed a negative correlation with sample storage time.Notably,in individuals without cognitive impairment,plasma levels of total protein and tau phosphorylated protein threonine 181(p-tau181)also showed a negative correlation with sample storage time.This was not observed in individuals with cognitive impairment.Consequently,we speculate that the diagnostic accuracy of plasma p-tau181 and the p-tau181 to total tau ratio may be influenced by sample storage time.Therefore,caution is advised when using these plasma biomarkers for the identification of neurodegenerative diseases,such as Alzheimer's disease.Furthermore,in cohort studies,it is important to consider the impact of storage time on the overall results.

Studies on the Relationship between Neuroendocrine Cellular Differentiation in Gastric Cancers and Post-operative Survival Time

OBJECTIVE To examine the ultrastructure of gastric cancer ceils by the electron microscope, in order to assess the relationship between neuroendocrine differentiation and post-operative survival time. METHODS NSE, Syn and CgA immunohistochemical labeling was conducted in 168 cases with a common-type of gastric cancer. Electron microscopy was performed in 80 cases with positive immunohistochemical labeling. These cases were followed-up for over 5 years and the post-operative survival data analyzed. RESULTS Neuroendocrine granules were found by electron microscopy in 39 cases. The rate of neuroendocrine differentiation found was 23% （39/168）, using routine diagnostic criteria and electron microscopy （REM）. The post-operative survival time of gastric cancer patients with neuroendocdne differentiation was significantly shorter （P=-0.0032） compared to those without neuroendocrine differentiation. CONCLUSION It is of significant clinical importance to determine if the neuroendocrine cells are differentiated in gastdc cancers. The gastric cancer patients with neuroendocrine differentiation have a shorter post-operative survival time and a poorer prognosis. Electron microscopy is a reliable method of providing a diagnosis.

Post-radiation survival time in hepatocellular carcinoma based on predictors for CT-determined, transarterial embolization and various other parameters

AIM: In this retrospective study of unresectable hepatocellular carcinoma (HCC), we have investigated the efficacy of CT-derived parameters, laboratory measurements, clinical assessment and associated transarterial embolization (TAE) as predictors of post-radiotherapy survival time. METHODS: Sixty-six patients diagnosed with unresectable HCC that had undergone radiotherapy at two medical university hospitals in Taipei were enrolled in the study. Using multivariant analysis, pre-treatment parameters including tumor number and CT confirmation of PVT and ascites were compared. Multivariant analysis was also used for comparison of the mean pretreatment values for laboratory measurements, including alpha-fetoprotein, direct/total bilirubin and GOT/GPT levels, and clinical history of chronic hepatitis across the three survival-time categories. The x2 was used to test the significance of the relationship between survival time and TAE procedure. The P values for the above tests were deemed statistically significant where P<0.05. RESULTS: Portal vein thrombosis (P= 0.032) and ascites (P><0.05) were negative predictors of post-radiation survival time. Low-grade liver cirrhosis (A or B), lower tumor volume and low levels of AFT, GOT/GPT, and total bilirubin were predictors of longer post-radiation survival time (P<0.05). CONCLUSION: The CT and clinical and laboratory assessment provide a reference for, and enable estimation of, probable survival times in HCC patients after radiotherapy. Tumor volume, severity of liver cirrhosis, status with respect to portal vein thrombosis and ascites and AFT, GOT/GPT and total bilirubin values were significant predictors of survival in this study.

The relationship between level of plasma D-dimer and survival time in metastatic gastric cancer patients

Objective:The principal purpose of this study was to determine the relationship between level of plasma D-dimer and survival time in metastatic gastric cancer patients.Methods:We retrospectively collected the data of plasma D-dimer in metastatic gastric cancer patients admitted in our Department (Department of Oncology,The Affiliated Changzheng Hospital,The Second Military Medical University,Shanghai,China) from October 2006 to October 2008 and analyzed the relationship between level of plasma D-dimer and survival time along with other clinicopathologic parameters.Results:A total of 82 patients were studied in our research,52 were males and 30 females,and the mean age was 57 years.The 48 cases had a normal plasma D-dimer level (<300μg/L) and 34 had a high plasma D-dimer level (≥300μg/L).In the normal and high plasma D-dimer level groups,the mean survival times were 10.9 (95% CI:9.8-12.2) months and 6.8(95% CI:4.4-7.6) months respectively,and the difference was statistically significant.Conclusion:Metastatic gastric cancer patients with high plasma D-dimer level had significantly shorter survival time than those with normal plasma D-dimer level.Level of plasma D-dimer can be referred as a potential predictor in metastatic gastric cancer patients.

Is there an optimal time to initiate adjuvant chemotherapy to predict benefit of survival in non-small cell lung cancer?

Objective: Adjuvant chemotherapy (AC) after curative resection is known to improve the survival of patients with non-small cell lung cancer (NSCLC); however, few studies have reported the correlation between the time to initiation of AC (TTAC) and survival in NSCLC patients. Methods: The clinical data of 925 NSCLC patients who received curative resection and post-operative AC at the Cancer Hospital of Chinese Academy of Medical Sciences between 2003 and 2013 were retrospectively analyzed. TTAC was measured from the date of surgery to the initiation of AC. Disease-free survival (DFS) was defined as the duration from surgery to the time of tumor recurrence or last follow-up evaluation. The optimal cut-off value of TTAC was determined by maximally selected log-rank statistics. The DFS curve was estimated using the Kaplan-Meier method, and the Cox proportional hazards regression model was used to identify risk factors independently associated with DFS. Propensity score matching (PSM) was performed for survival analysis using the match data. Results: The optimal discriminating cut-off value of TTAC was set at d 35 after curative resection based on which the patients were assigned into two groups: group A (<= 35 d) and group B (> 35 d). There was no significant difference in the DFS between the two groups (P=0.246), indicating that the TTAC is not an independent prognostic factor for DFS. A further comparison continued to show no significant difference in the DFS among 258 PSM pairs (P=0.283). Conclusions: There was no significant correlation between the TTAC and DFS in NSCLC patients. Studies with larger samples are needed to further verify this conclusion.

4种植物源性成分多重real-time PCR检测方法的建立及其在食用淀粉中的应用

建立一种可同时快速检测红薯、木薯、马铃薯、玉米源性成分的多重实时聚合酶链式反应(real-time polymerase chain reaction,real-time PCR)方法。分别以红薯g3pdh基因、木薯g3pdh基因、马铃薯UGPase基因、玉米zSSIIb基因为靶基因设计特异性引物和TaqMan探针,以18S rRNA基因为内参基因,建立多重real-time PCR方法,开展方法学验证,并对不同掺入比例模拟样品和实际淀粉样品进行检测。结果显示,该方法具有高通量、特异性强、灵敏度高等优点。与15种非目标源性均无交叉反应;对目标DNA的检测灵敏度可达到3×10^(-3) ng/μL,且具有良好的线性关系和扩增效率;对淀粉样品的检出限可达0.1%,对50份实际样品进行检测,结果与参比方法一致,说明建立的多重real-time PCR法可用于食用淀粉种类掺假鉴别检测。

Bayesian Joint Modelling of Survival Time and Longitudinal CD4 Cell Counts Using Accelerated Failure Time and Generalized Error Distributions

Survival of HIV/AIDS patients is crucially dependent on comprehensive and targeted medical interventions such as supply of antiretroviral therapy and monitoring disease progression with CD4 T-cell counts. Statistical modelling approaches are helpful towards this goal. This study aims at developing Bayesian joint models with assumed generalized error distribution (GED) for the longitudinal CD4 data and two accelerated failure time distributions, Lognormal and loglogistic, for the survival time of HIV/AIDS patients. Data are obtained from patients under antiretroviral therapy follow-up at Shashemene referral hospital during January 2006-January 2012 and at Bale Robe general hospital during January 2008-March 2015. The Bayesian joint models are defined through latent variables and association parameters and with specified non-informative prior distributions for the model parameters. Simulations are conducted using Gibbs sampler algorithm implemented in the WinBUGS software. The results of the analyses of the two different data sets show that distributions of measurement errors of the longitudinal CD4 variable follow the generalized error distribution with fatter tails than the normal distribution. The Bayesian joint GED loglogistic models fit better to the data sets compared to the lognormal cases. Findings reveal that patients’ health can be improved over time. Compared to the males, female patients gain more CD4 counts. Survival time of a patient is negatively affected by TB infection. Moreover, increase in number of opportunistic infection implies decline of CD4 counts. Patients’ age negatively affects the disease marker with no effects on survival time. Improving weight may improve survival time of patients. Bayesian joint models with GED and AFT distributions are found to be useful in modelling the longitudinal and survival processes. Thus we recommend the generalized error distributions for measurement errors of the longitudinal data under the Bayesian joint modelling. Further studies may investigate the models with various types of shared random effects and more covariates with predictions.

Reverse time-dependent effect of alphafetoprotein and disease control on survival of patients with Barcelona Clinic Liver Cancer stage C hepatocellular carcinoma

AIM To characterize the survival of cirrhotic patients with Barcelona Clinic Liver Cancer(BCLC) stage C hepatocellular carcinoma(HCC) and to ascertain the factors predicting the achievement of disease control(DC).METHODS The cirrhotic patients with BCLC stage C HCC evaluated by the Hepatocatt multidisciplinary group were subjected to the investigation. Demographic, clinical and tumor features, along with the best tumor response and overall survival were recorded. RESULTS One hundred and ten BCLC stage C patients were included in the analysis; the median overall survival was 13.4 mo(95%CI: 10.6-17.0). Only alphafetoprotein(AFP) serum level > 200 ng/m L and DC could independently predict survival but in a time dependent manner, the former was significantly associated with increased risk of mortality within the first 6 mo of follow-up(HR = 5.073, 95%CI: 2.159-11.916, P = 0.0002), whereas the latter showed a protective effect against death after one year(HR = 0.110, 95%CI: 0.038-0.314, P < 0.0001). Only patients showing microvascular invasion and/or extrahepatic spread recorded lower chances of achieving DC(OR = 0.263, 95%CI: 0.111-0.622, P = 0.002).CONCLUSION The BCLC stage C HCC includes a wide heterogeneous group of cirrhotic patients suitable for potentially curative treatments. The reverse and time dependent effect of AFP serum level and DC on patients' survival confers them as useful predictive tools for treatment management and clinical decisions.

Analysis of Influencing Factors on Survival Time of Patients with Heart Failure

To explore the influencing factors of survival time of patients with heart failure, a total of 1789 patients with heart failure were collected from Shanghai Shuguang Hospital. The Cox proportional hazards model and the mixed effects Cox model were used to analyze the factors on survival time of patients. The results of Cox proportional hazards model showed that age (RR = 1.32), hypertension (RR = 0.67), ARB (RR = 0.55), diuretic (RR = 1.48) and antiplatelet (RR = 0.53) have significant impacts on the survival time of patients. The results of mixed effects Cox model showed that age (RR = 1.16), hypertension (RR = 0.61), lung infection (RR = 1.43), ARB (RR = 0.64), β-blockers (RR = 0.77) and antiplatelet (RR = 0.69) have a significant impact on the survival time of patients. The results are consistent with the covariates age, hypertension, ARB and antiplatelet but inconsistent with the covariates lung infection and β-blockers.

A COMPARATIVE STUDY ON THERAPEUTIC RESPONSE AND SURVIVAL TIME OF PATIENTS WITH MULTIPLE MYELOMA TREATED WITH MODIFIED VMCP REGIMEN

Therapeutic response and survival time or 43 patients with multiple myeloma treated with modified VMCP(Vincristine,Melphalan, Cyelophosphamide and perdnisone;mVMCP)multidrug regimen are analyzed,and compared with those of 41 patients treated with VACP, M2, MP and other regimens.Therapeutic response to mVMCP regimen was better than that to other combination regimens(83. 5% VS 60.9%;P< 0.01).The median remission duration in patients responding to mVMCP was longer than that to other regimens(18.7 vs 12.2 mouths;P<0.001).But the survival time of two groups of responders was not signifficautly different(32. 5 vs 34.1 mouths; P>0.5).The prognostic significance of various pretreatment characteristics was evaluated in term of therapeutic response.The bone status and renal function had a significant inverse correlation with the survival time of patients responding to chemotherapy.Our data indicate that the patients with MM treated by mean or mVMCP regimen can obtain a better response in early treatment and maintain a longer remission duration as well as a better performance status. although the regimen can not prolong the patients survival time.

ICON/MIGHTI与TIMED/SABER探测温度数据的对比

ICON卫星为临近空间环境特性研究、建模和预报提供了新数据.通过对ICON/MIGHTI与TIMED/SABER在90~105 km高度探测温度数据的比较,计算两者的年平均温度偏差和均方根误差,同时分析月平均温度偏差在不同月份中随高度和纬度的分布情况,为MIGHTI和SABER温度探测数据在临近空间大气建模和预报应用提供参考依据.结果表明,MIGHTI和SABER的温度垂直廓线变化趋势基本吻合,数值上有所差异.在12°S-42°N范围内,MIGHTI探测温度与SABER相比,在90~93 km时偏低,偏差最大值约2.5 K,在93~105 km偏高,偏差的绝对值最大约10 K.在不同季节,白天的温度偏差通常高于夜晚.SABER和MIGHTI的月平均温度偏差随季节和纬度的变化显著,夏季时的月平均温度偏差最大,且温度的均方根误差最大.

Partition-Time Masking:一种唇语识别数据增强方法

提出了一种唇语识别数据增强方法Partition-Time Masking。该方法直接作用于输入数据,通过将输入划分为多个子序列再分别进行Mask操作最后再将各子序列按序拼接,使得模型能对部分帧缺失的输入具有更强的鲁棒性,从而增强泛化能力。实验前根据划分的子序列数目与掩码值来源不同而设计了5种增强策略,并与唇语识别研究中最重要的数据增强方法Time Masking进行了对比实验。实验在LRW数据集和LRW1000数据集上进行,实验结果表明Partition-Time Masking方法对模型性能提升的效果要优于Time Masking方法,其中子序列数目为3、掩码值选择各子序列平均帧时为最优策略,该策略使得目前最佳的唇语识别模型DC-TCN的性能从89.6%提高到90.0%。

Lag time,high-risk histopathological features,metastasis,and survival interrelation in retinoblastoma:a perspective from lower-middle income country

AIM:To investigate the impact of lag time to metastasis and survival rates among patients with retinoblastoma.METHODS:This retrospective study was conducted with 52 patients from the Department of Ophthalmology and the Department of Pediatrics of Dr.Sardjito General Hospital,between 1^(st) January 2014 and 31^(st) December 2020.Lag time was defined as the time delay between the first sign of retinoblastoma to the diagnosis of retinoblastoma.The subjects with lag time>one year were included in the case group,while the subjects with lag time<one year were included in the control group.RESULTS:The lag time was significantly correlated with American Joint Committee on Cancer and Intraocular Classification of Retinoblastoma staging of retinoblastoma(P=0.005 and P=0.006,respectively).The lag time was also significantly correlated with both metastasis event[odds ratio(OR):5.06,95%Cl:1.56-16.44,P=0.006]and mortality(OR:4.54,95%Cl:1.37-15.07,P=0.011).The follow-up was continued for 32 subjects for 3y after initial diagnoses.Survival analysis revealed a significant difference among these two groups(P=0.021).Furthermore,lag time was significantly correlated with survival of retinoblastoma(r=-0.53,P=0.046).CONCLUSION:The study highlights the importance of lag time between the onset of first symptoms and the time of retinoblastoma diagnosis which significantly contribute to metastasis and mortality of patients with retinoblastoma.Examinations for the early detection of retinoblastoma should be performed for individuals at-risk to minimize lag time and improve the outcomes.

The Correlation of Lung Function Indexes and Survival Time of Patients with Advanced Lung Cancer

Background: To those patients with advanced lung cancer, the ultimate objective is to improve the quality of life, and lung function is an important factor affecting quality of life. We detect lung function of patients with lung cancer and study the correlation between lung function and the patients’ survival time, to provide reference for evaluation of disease progression and prognosis. Methods: Lung function was detected on 59 cases of lung cancer and 63 normal controls. The relationship between lung function indexes and survival time was analyzed. Results: There was significant difference in ventilation function and diffusing capacity between lung cancer group and control group. Vital capacity (VC), Forced expiratory volume in one second (FEV1), Forced vital capacity (FVC), peak expiratory flow (PEF), peak expiratory flow% (PEF%), Maximal ventilatory volume (MVV) were positively correlated to survival time in patients with advanced lung cancer (r = 0.28522064, 0.28053851, 0.28289252, 0.26908133, 0.26335034, 0.28409036, P 0.05), residual volume/total lung capacity was negatively correlated to survival time (r = ?0.30760097, P 0.05). Conclusions: The lung function decrease in the patients with lung cancer. Vital capacity (VC), Forced expiratory volume in one second (FEV1), Forced vital capacity (FVC), peak expiratory flow (PEF), peak expiratory flow% (PEF%), Maximal ventilatory volume (MVV), and residual volume/total lung capacity are correlated to survival time in patients with advanced lung cancer. The lung function indexes are important marker of prognosis of patients with lung cancer.

Predictive formulas expressing relationship between dose rate and survival time in total body irradiation in mice

The Gompertz model is the long-time well-known mathematical model of exponential expression among mortality models in the literature that are used to describe mortality and survival data of a population. The death rate of the “probacent” model developed by the author based on animal experiments, clinical applications and mathematical reasoning was applied to predict age-specific death rates in the US elderly population, 2001, and to express a relationship among dose rate, duration of exposure and mortality probability in total body irradiation in humans. The results of both studies revealed a remarkable agreement between “probacent”-formula-predicted and published-reported values of death rates in the US elderly population or mortality probabilities in total body irradiation in humans (p - value > 0.995 in χ2 test in each study). In this study, both the Gompertz and “probacent” models are applied to the Sacher’s comprehensive experimental data on survival times of mice daily exposed to various doses of total body irradiation until death occurs with an assumption that each of both models is applicable to the data. The purpose of this study is to construct general formulas expressing relationship between dose rate and survival time in total body irradiation in mice. In addition, it is attempted to test which model better fits the reported data. The results of the comparative study revealed that the “probacent” model not only fit the Sacher’s reported data but also remarkably better fit the reported data than the Gompertz model. The “probacent” model might be hopefully helpful in research in human tolerance to low dose rates for long durations of exposure in total body irradiation, and further in research in a variety of biomedical phenomena.

TimeGAN-Informer长时机场能见度预测

能见度的预测对机场的业务决策、保障飞机的安全起降具有重要的意义。针对现有能见度预测模型预测时间较短的问题,提出一种基于TimeGAN Informer(Time Generative Adversarial Network-Informer)的机场能见度预测方法。利用2018—2022年气象和污染物数据,通过相关系数法和递归特征消除法提取出能见度的主要影响因素,使用TimeGAN时间序列生成对抗网络对数据进行扩充,并将Informer长时间序列预测模型应用于能见度预测。结果显示:当预测步长为1 d、2 d、3 d时,TimeGAN Informer的绝对误差(Mean Absolute Error,MAE)分别为2.42、3.13、3.57,比Informer分别降低了0.29、0.27、0.28,比长短时记忆网络(Long Short-Term Memory,LSTM)分别降低了0.28、0.49、0.63;均方根误差(Root Mean Square Error,RMSE)分别为3.03、3.7、4.09,比Informer分别降低了0.38、0.22、0.24,比长短时记忆网络(LSTM)分别降低了0.3、0.5、1.04;百分误差小于30%的分别占测试样本集的78.07%、70.68%、63.84%。尽管随着步长的增加预测效果变差,但在预测步长为3 d时,多数样本的预测误差仍小于30%,实现了对机场区域较为准确的长时能见度预测。

A Measure for Assessing Functions of Time-Varying Effects in Survival Analysis

A standard approach for analyses of survival data is the Cox proportional hazards model. It assumes that covariate effects are constant over time, i.e. that the hazards are proportional. With longer follow-up times, though, the effect of a variable often gets weaker and the proportional hazards (PH) assumption is violated. In the last years, several approaches have been proposed to detect and model such time-varying effects. However, comparison and evaluation of the various approaches is difficult. A suitable measure is needed that quantifies the difference between time-varying effects and enables judgement about which method is best, i.e. which estimate is closest to the true effect. In this paper we adapt a measure proposed for the area between smoothed curves of exposure to time-varying effects. This measure is based on the weighted area between curves of time-varying effects relative to the area under a reference function that represents the true effect. We introduce several weighting schemes and demonstrate the application and performance of this new measure in a real-life data set and a simulation study.

Coping styles as predictors of survival time in bladder cancer

The role of coping in the survival of cancer is a controversial topic. To specifiy the influence of coping on survival time, we conducted a longitudinal, prospective and observational study. In a preoperative interview, 105 patients with primary bladder cancer were asked about their active and depressive coping strategies. Ten years later, the survival rate was recorded;in cases of death, it was noted whether or not it was in consequence of the bladder cancer. Kaplan-Meier analyses of the collected data revealed a mean survival rate of about 60% after 10 years. Cox regression demonstrated no significant effect for active or depressive coping when tumour stage was controlled for. Patients who presented with high values for either of the coping strategies lived only slightly longer than those with low values. Therefore, it can be concluded that preoperative coping does not seem to demonstrate an important role for survival in bladder cancer.

A Comparison of Within-Subjects and Between-Subjects Designs in Studies with Discrete-Time Survival Outcomes

Crossover designs are well-known to have major advantages when comparing the effects of various non-curative treatments. We compare efficiencies of several crossover designs along with the Balaam’s design with that of a parallel group design pertaining to longitudinal studies where event time can only be measured in discrete time intervals. With equally sized sequences, the parallel group design results in the greater efficiency if the number of time periods is small. However, the crossover and Balaam’s designs tend to be more efficient as the study duration increases. The degree to which these designs add efficiency depends on the baseline hazard function and effect size. Additionally, we incorporate different cost considerations at the subject level when comparing the designs to determine the most cost-efficient design. Researchers might consider the crossover or Balaam’s design more efficient if the duration of the study is long enough, especially if the costs of applying the baseline treatment are higher.

基于TimeGAN数据增强的复杂过程故障分类方法

针对传统基于重构的故障分类方法在故障样本稀疏或失衡情况下效果不佳、故障子空间区分能力弱的问题,提出基于TimeGAN数据增强的复杂过程故障分类方法.针对小子样故障,使用TimeGAN对历史故障数据进行数据增强,生成与历史数据分布相似的虚拟故障样本;采用马氏距离评估虚拟样本的质量,剔除不可信样本,构造平衡的故障样本集.将故障样本映射到高维核空间,并在核空间中提取故障子空间.设计故障分类策略并定义4种故障分类性能评估指标以定量衡量算法的分类性能.Tennessee Eastman应用结果表明,所提数据增强方法可以有效扩充故障样本,进而提高故障重构率.与WGAN-GP和SMOTE方法进行对比,发现基于TimeGAN数据增强的故障分类方法具有更好的分类性能.