The T790M mutation is the major resistance mechanism to first- and second-generation TKIs in EGFR-mutant NSCLC. This study aimed to investigate the utility of droplet digital PCR (ddPCR) for ...detection of T790M in plasma circulating tumor DNA (ctDNA), and explore its impact on prognosis.
This prospective study enrolled 80 advanced lung adenocarcinoma patients treated with gefitinib, erlotinib, or afatinib for TKI-sensitizing mutations between 2015 and 2019. Plasma samples were collected before TKI therapy and at tri-monthly intervals thereafter. Genotyping of ctDNA for T790M was performed using a ddPCR EGFR Mutation Assay. Patients were followed up until the date of death or to the end of 2021.
Seventy-five of 80 patients experienced progressive disease. Fifty-three (71%) of 75 patients underwent rebiopsy, and T790M mutation was identified in 53% (28/53) of samples. Meanwhile, plasma ddPCR detected T790M mutation in 23 (43%) of 53 patients. The concordance rate of T790M between ddPCR and rebiopsy was 76%, and ddPCR identified 4 additional T790M-positive patients. Ten (45%) of 22 patients who did not receive rebiopsy tested positive for T790M by ddPCR. Serial ddPCR analysis showed the time interval from detection of plasma T790M to objective progression was 1.1 (0-4.1) months. Compared to 28 patients with rebiopsy showing T790M, the overall survival of 14 patients with T790M detected solely by ddPCR was shorter(41.3 95% CI, 36.6-46.0 vs. 26.6 months 95% CI, 9.9-43.3, respectively).
Plasma ddPCR-based genotyping is a useful technology for detection and monitoring of the key actionable genomic alteration, namely, T790M, in patients treated with gefitinib, erlotinib, or afatinib for activating mutations, to achieve better patient care and outcome.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We investigated whether microRNA expression profiles can predict clinical outcome of NSCLC patients. Using real-time RT-PCR, we obtained microRNA expressions in 112 NSCLC patients, which were divided ...into the training and testing sets. Using Cox regression and risk-score analysis, we identified a five-microRNA signature for the prediction of treatment outcome of NSCLC in the training set. This microRNA signature was validated by the testing set and an independent cohort. Patients with high-risk scores in their microRNA signatures had poor overall and disease-free survivals compared to the low-risk-score patients. This microRNA signature is an independent predictor of the cancer relapse and survival of NSCLC patients.
This article presents a synchronization control method based on poles' placement, disturbances, and uncertainty estimation (DUE) for a pair of Takagi-Sugeno fuzzy systems. First, a 3-D chaotic system ...was completely converted into a Takagi-Sugeno (T-S) fuzzy model by applying the nonlinearity sector method, which consists of if-then rules and sub-linear systems. Second, two identical T-S fuzzy systems with different initial conditions were synchronized by applying the linear matrix inequality (LMI) to place the eigenvalues of the state error equations in the stable region. Third, the sum of the time-varying disturbances and uncertainties of two nonidentical T-S fuzzy systems were deleted by a disturbance and uncertainty estimation. The given output signals confirmed that the proposed method is suitable and ideal for synchronizing T-S fuzzy systems. The ideas of control theory were implemented by using two experimental scenarios in MATLAB Simulink for two computers connected via an internet router and an electronics circuit's communication.
•Adenocarcinoma can transform into SCLC as a mechanism of resistance to TKIs.•We investigated genetic profiles of combined SCLC/NSCLC patients.•SCLC and NSCLC components showed a high consistency in ...EGFR/TP53/RB1 mutations.•TP53/RB1 inactivation may be an early event in the tumorigenesis of combined SCLC/NSCLC.•The SCLC component may arise from NSCLC via activation of the ASCL1 pathway and PI3K/AKT1 signaling pathway.
Histologic transformation from adenocarcinoma to small cell lung cancer (SCLC) is one of the mechanisms of acquired resistance after epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment. Furthermore, de novo combined SCLC/non-small cell lung cancer (NSCLC) have occasionally been reported; however, their mutational statuses and clinicopathological features have not yet been elucidated. In this study, we aimed to profile the genetic backgrounds of these 2 different histologic components by investigating patients with de novo combined SCLC/NSCLC as well as those with lung adenocarcinoma who experienced SCLC transformation after TKI treatment.
Four patients with de novo combined SCLC/NSCLC were investigated, as were 4 other patients with lung adenocarcinoma who experienced SCLC transformation after TKI treatment. The different histologic components of the tumors in each patient were tested for thyroid transcription factor-1, p40, synaptophysin, chromogranin A, p53, retinoblastoma protein (Rb), and achaete-scute homolog 1 (ASCL1) via immunohistochemistry, and were macroscopically dissected for mutational analysis using next-generation sequencing with the Oncomine Focus Assay and Comprehensive Assay panel.
The distinct histologic components in patients with de novo combined SCLC/NSCLC and those with adenocarcinoma exhibiting small cell transformation showed high consistency in EGFR/TP53/RB1 mutations, and expression patterns of p53 and Rb. A high frequency of activating mutations involving PI3K/AKT1 signaling pathway was observed in SCLC. Nuclear ASCL1 expression was present in SCLC but absent or barely present in adenocarcinoma in 7 cases.
Our data imply that inactivation of TP53/RB1 function is a possible early event in the histogenesis of synchronous and metachronous SCLC/NSCLC. Moreover, the non-adenocarcinoma (SCLC) component might arise from the adenocarcinoma (NSCLC) component through a mechanism that involves the activation of the ASCL1 and PI3K/AKT1 signaling pathways.
In recent years, hypertension has become one of the leading causes of illness and death worldwide. Changes in lifestyle among the population have led to an increasing prevalence of hypertension. This ...study proposes a non-contact blood pressure estimation method that allows patients to conveniently monitor their blood pressure values. By utilizing a webcam to track facial features and the region of interest (ROI) for obtaining forehead images, independent component analysis (ICA) is employed to eliminate artifact signals. Subsequently, physiological parameters are calculated using the principle of optical wave reflection. The Nelder–Mead (NM) simplex method is combined with the particle swarm optimization (PSO) algorithm to optimize the empirical parameters, thus enhancing computational efficiency and accurately determining the optimal solution for blood pressure estimation. The influences of light intensity and camera distance on the experimental results are also discussed. Furthermore, the measurement time is only 10 s. The superior accuracy and efficiency of the proposed methodology are demonstrated by comparing them with those in other published literature.
This paper presents a robust control methodology based on a disturbance observer and an optimal states feedback for Takagi–Sugeno fuzzy system. Firstly, the nonlinear systems were solved by applying ...a sector nonlinearity method to get the inner linear subsystems and outer fuzzy membership functions, which guaranteed the conversion without any loss generality characteristics of the system. Secondly, an exponentially convergent disturbance observer was constructed to the system with an assumption that the system states are temporarily bounded. Thirdly, a states observer was built by poles placement of linear quadratic regulation optimization, which was used to place the system states error poles located on the stable region. Finally, simulation examples were given to figure out that the proposed controller is effective to control the Takagi–Sugeno fuzzy system. The obtained results are disturbance mostly rejected, state estimation errors are quite small, and the output signal precisely tracked input signal.
Cardiorespiratory endurance refers to the ability of the heart and lungs to deliver oxygen to working muscles during continuous physical activity, which is an important indicator of physical health. ...Cardiorespiratory endurance is typically measured in the laboratory by maximum oxygen uptake (VO
) which is not a practical method for real-life use. Given the relative difficulty in measuring oxygen consumption directly, we can estimate cardiorespiratory endurance on the basis of heart beat. In this paper, we proposed a fuzzy system based on the human heart rate to provide an effective cardiorespiratory endurance training program and the evaluation of cardiorespiratory endurance levels. Trainers can respond correctly with the help of a smart fitness app to obtain the desired training results and prevent undesirable events such as under-training or over-training. The fuzzy algorithm, which is built for the Android mobile phone operating system receives the resting heart rate (RHR) of the participants via Bluetooth before exercise to determine the suitable training speed mode of a treadmill for the individual. The computer-based fuzzy program takes RHR and heart rate recovery (HRR) after exercise as inputs to calculate the cardiorespiratory endurance level. The experimental results show that after 8 weeks of exercise training, the RHR decreased by an average of 11%, the HRR increased by 51.5%, and the cardiorespiratory endurance evaluation level was also improved. The proposed system can be combined with other methods for fitness instructors to design a training program that is more suitable for individuals.
No published studies to date have evaluated the detailed pathologic and genetic features of lung adenocarcinoma after epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy ...and salvage surgery. We aimed to evaluate the pathologic and genetic changes of tumors in patients with advanced lung adenocarcinoma treated with EGFR TKI therapy and salvage surgery.
This study retrospectively collected data from 29 advanced lung adenocarcinoma patients who underwent EGFR TKI therapy, followed by salvage operation, between January 2010 and December 2018. All patients had partial response or stable disease without evidence of progressive disease. Next-generation sequencing was used to determine whether acquired resistant mutations in morphologically treatment-sensitive and morphologically treatment-resistant regions of tumor existed.
There were 3, 22, and 4 patients with clinical stage IIIB, IVA, and IVB, respectively. After a mean TKI treatment duration of 134 days, 27 patients had partial response, 2 had stable disease, and 27.6% of patients were downstaged before salvage surgery. All patients had residual viable tumor cells in their tumor bed; 5 patients (17.2%) had a major pathologic response. Acquired T790M mutations (n = 4), histologic transformations (n = 2), and acquired T790M mutation with histologic transformation (n = 1) were identified in the morphologically treatment-resistant regions of tumors. The 3-year overall survival was 75.9%.
The presence of morphologically treatment-resistant tumor regions with acquired T790M mutations and histologic transformations demonstrate the existence of resistant subclones in TKI-treated tumors before disease progression. Salvage surgery performed in selected patients before disease progression may improve survival by removing TKI-resistant subclones.
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At present, when traditional industries process a large amount of data and key data are combined with specific technologies and management skills, a lot of manpower is required for data processing or ...decision-making work analysis. However, within the background of information technology, sensing components and various decision-making calculations are mature, and a manufacturing system that uses a large amount of advanced sensor software of the graphical user interface (GUI) and hardware systems of, for example, photoelectric, registration mark, color and luminescence, pick-to-light, and temperature vibration sensors can become more and more intelligent and capable of replacing some human expertise. Intelligent manufacturing is expected to improve the efficiency of the whole production process, provide timely production technology, complete the production schedule, control the accuracy of the delivery date, and devise effective countermeasures in accordance with market changes at any time. Therefore, a digital transformation system solution is proposed for enterprise problems or the development of bottlenecks, so that the digital level of the entire industry operation can be improved. Therefore, it is expected that Microsoft's Power Business Intelligence (PBI) can be utilized to visualize and present the data imported from Excel, allowing the production data to be transformed into easily readable charts. This enables the real-time monitoring of on-site information, ensures the proper material coordination, and achieves Just-In-Time (JIT) production. By adopting this approach, enterprises can easily implement intelligent manufacturing, improve work efficiency, reduce the cost of acquiring visualization systems, and enable managers to have real-time insights into the current operational status of the company. This reduces the need for substantial investment in funds and manpower, allowing companies to allocate resources in accordance with their needs and accelerate the transformation into the era of smart manufacturing.
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