Multipathway regulation induced by 4-(phenylsulfonyl)morpholine derivatives against triple-negative breast cancer.

Phenotypic drug discovery (PDD) is an effective drug discovery approach by observation of therapeutic effects on disease phenotypes, especially in complex disease systems. Triple-negative breast cancer (TNBC) is composed of several complex disease features, including high tumor heterogeneity, high invasive and metastatic potential, and a lack of effective therapeutic targets. Therefore, identifying effective and novel agents through PDD is a current trend in TNBC drug development. In this study, 23 novel small molecules were synthesized using 4-(phenylsulfonyl)morpholine as a pharmacophore. Among these derivatives, GL24 (4m) exhibited the lowest half-maximal inhibitory concentration value (0.90 µM) in MDA-MB-231 cells. To investigate the tumor-suppressive mechanisms of GL24, transcriptomic analyses were used to detect the perturbation for gene expression upon GL24 treatment. Followed by gene ontology (GO) analysis, gene set enrichment analysis (GSEA), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, multiple ER stress-dependent tumor suppressive signals were identified, such as unfolded protein response (UPR), p53 pathway, G2/M checkpoint, and E2F targets. Most of the identified pathways triggered by GL24 eventually led to cell-cycle arrest and then to apoptosis. In summary, we developed a novel 4-(phenylsulfonyl)morpholine derivative GL24 with a strong potential for inhibiting TNBC cell growth through ER stress-dependent tumor suppressive signals.

Utilizing a Two-Stage Taguchi Method and Artificial Neural Network for the Precise Forecasting of Cardiovascular Disease Risk.

The complexity of cardiovascular disease onset emphasizes the vital role of early detection in prevention. This study aims to enhance disease prediction accuracy using personal devices, aligning with point-of-care testing (POCT) objectives. This study introduces a two-stage Taguchi optimization (TSTO) method to boost predictive accuracy in an artificial neural network (ANN) model while minimizing computational costs. In the first stage, optimal hyperparameter levels and trends were identified. The second stage determined the best settings for the ANN model's hyperparameters. In this study, we applied the proposed TSTO method with a personal computer to the Kaggle Cardiovascular Disease dataset. Subsequently, we identified the best setting for the hyperparameters of the ANN model, setting the hidden layer to 4, activation function to tanh, optimizer to SGD, learning rate to 0.25, momentum rate to 0.85, and hidden nodes to 10. This setting led to a state-of-the-art accuracy of 74.14% in predicting the risk of cardiovascular disease. Moreover, the proposed TSTO method significantly reduced the number of experiments by a factor of 40.5 compared to the traditional grid search method. The TSTO method accurately predicts cardiovascular risk and conserves computational resources. It is adaptable for low-power devices, aiding the goal of POCT.

Upper-Arm Photoplethysmographic Sensor with One-Time Calibration for Long-Term Blood Pressure Monitoring.

Wearable cuffless photoplethysmographic blood pressure monitors have garnered widespread attention in recent years; however, the long-term performance values of these devices are questionable. Most cuffless blood pressure monitors require initial baseline calibration and regular recalibrations with a cuffed blood pressure monitor to ensure accurate blood pressure estimation, and their estimation accuracy may vary over time if left uncalibrated. Therefore, this study assessed the accuracy and long-term performance of an upper-arm, cuffless photoplethysmographic blood pressure monitor according to the ISO 81060-2 standard. This device was based on a nonlinear machine-learning model architecture with a fine-tuning optimized method. The blood pressure measurement protocol followed a validation procedure according to the standard, with an additional four weekly blood pressure measurements over a 1-month period, to assess the long-term performance values of the upper-arm, cuffless photoplethysmographic blood pressure monitor. The results showed that the photoplethysmographic signals obtained from the upper arm had better qualities when compared with those measured from the wrist. When compared with the cuffed blood pressure monitor, the means ± standard deviations of the difference in BP at week 1 (baseline) were -1.36 ± 7.24 and -2.11 ± 5.71 mmHg for systolic and diastolic blood pressure, respectively, which met the first criterion of ≤5 ± ≤8.0 mmHg and met the second criterion of a systolic blood pressure ≤ 6.89 mmHg and a diastolic blood pressure ≤ 6.84 mmHg. The differences in the uncalibrated blood pressure values between the test and reference blood pressure monitors measured from week 2 to week 5 remained stable and met both criteria 1 and 2 of the ISO 81060-2 standard. The upper-arm, cuffless photoplethysmographic blood pressure monitor in this study generated high-quality photoplethysmographic signals with satisfactory accuracy at both initial calibration and 1-month follow-ups. This device could be a convenient and practical tool to continuously measure blood pressure over long periods of time.

Optimizing Optical Film Lamination to Enhance the Luminance of TFT-LCD Displays Using the Taguchi-NNGA Method.

Luminance is an essential quality of a TFT-LCD display. Manufacturers have attempted to improve the soft-to-hard lamination stage to enhance the luminance of their TFT-LCD displays. In addition, many customers have complained about the insufficient luminance of the TFT-LCD displays of the case company. While product engineers have kept tuning the control factors in the soft-to-hard lamination stage through the trial and error method, the improvement of the luminance was not good enough. This study aims to assist the product engineers to fine-tune the settings of the control factors using a new method composed of the Taguchi method, a neural network, and a genetic algorithm. The confirmation experiments showed that the proposed method had increased the average luminance of the TFT-LCD displays from 17.03 to 25.15, which was higher than the required luminance value of 25. As a result, the number of complaints on the TFT-LCD displays had been significantly reduced.

Practical Suitability of a Stand-Alone Oscillometric Central Blood Pressure Monitor: A Review of the Microlife WatchBP Office Central.

Accumulating evidence indicates that central blood pressure (CBP) is a better cardiovascular risk predictor than brachial blood pressure (BP). Although more additional benefits of CBP-based treatment above usual hypertension treatment are to be demonstrated, the demand for implementing CBP assessment in general clinical practice is increasing. For this, the measurement procedure must be noninvasive, easy to perform, and cost- and time-efficient. Therefore, oscillometric devices with the possibility to assess CBP seem the best option. Recently, such an oscillometric BP monitor, the Microlife WatchBP Office Central, was developed, which demonstrated its high accuracy in a validation study against invasive BP measurement. Calibration errors of this device are limited because the procedure is automated, standardized, and performed at the same place of and within 30 s from pulse wave assessment. The transformation from the peripheral pulse wave to CBP is done by means of an individual-based pulse wave analysis according to a theory of arterial compliance and wave reflections. In addition, the device has demonstrated to enable a more reliable diagnosis of hypertension by CBP than by peripheral BP, with a lower frequency of over- and underdiagnosis. Altogether, the available clinical evidence suggests that the Microlife WatchBP Office Central fulfills the criteria for general clinical use.

Innovative light collimator with afocal lens and total internal reflection lens for daylighting system.

This research presents a novel design of the collimator, which uses total internal reflection (TIR), convex, and concave lenses for the natural light illumination system (NLIS). The concept of the NLIS is to illuminate building interiors with natural light, which saves energy consumption. The TIR lens is used to collimate the light, and convex and concave lenses are used to converge the light to the required area. The results have shown that the efficiency in terms of achieving collimated light using the proposed collimator at the output of the light collector is better than that of a previous system without a collimator.

Automated device that complies with current guidelines for office blood pressure measurement: design and pilot application study of the Microlife WatchBP Office device.

OBJECTIVE: Current guidelines for office blood pressure (BP) measurement recommend mercury devices, both arms measurement in the initial assessment and at least duplicate measurements at follow-up visits. This study presents the design and a pilot application study of an automated device that fulfils American, European, and International guidelines for office BP measurement. DESIGN AND FUNCTIONS: The Microlife WatchBP Office is a professional electronic mercury-free device with three function modes designed for: (a) initial assessment: triplicate automated simultaneous oscillometric both arms measurement at 60-s intervals and when there is a consistent interarm difference more than 20 mmHg systolic and/or more than 10 mmHg diastolic, the arm with the higher BP is indicated. (b) Follow-up assessment: triplicate automated oscillometric single arm measurements at 60-s intervals and their average is displayed. (c) Auscultatory measurement: by an observer using a stethoscope and a digital countdown BP display for patients with arrhythmias and other individuals in whom the oscillometric measurement is not accurate. PILOT APPLICATION STUDY: The 'initial assessment' mode was applied by three physicians in 63 patients (189 readings). Average interarm systolic BP difference was 0.04+/-5.1 mmHg and diastolic 0.4+/-3.2 mmHg. A value more than 10 mmHg interarm difference in nine systolic BP readings (5%) and three (2%) diastolic. No patient had a consistent interarm difference more than 10 mmHg in all three or two of the three readings. CONCLUSION: The Microlife WatchBP Office professional device fulfils current international requirements for office BP measurement and seems to overcome several limitations of this method when applied in clinical practice.