Comparative Efficacy and Safety of Standard and Biweekly Trifluridine/Tipiracil Regimen in Patients With Colorectal Cancer.

BACKGROUND/AIM: Trifluridine/tipiracil (FTD/TPI) is used to treat metastatic colorectal cancer (mCRC). Since the standard regimen of FTD/TPI features a complex dosing schedule and frequently results in severe hematological toxicities, a simplified regimen has emerged, in which FTD/TPI is orally administered biweekly. However, the survival benefits and potential adverse events associated with the biweekly FTD/TPI regimen have not been fully evaluated in previous reports. Therefore, in this study, the differences in efficacy and safety between the standard and biweekly FTD/TPI regimens were retrospectively investigated in patients with mCRC. PATIENTS AND METHODS: Data from 90 patients who received FTD/TPI for mCRC were extracted from the electronic medical records at the Osaka University Hospital. According to the inclusion and exclusion criteria, 85 of the 90 patients were enrolled in the study. We compared patient characteristics, overall survival (OS), progression-free survival (PFS), and adverse events between the standard (n=56) and biweekly groups (n=29). RESULTS: The biweekly group exhibited prolonged OS and PFS compared to patients in the standard group. Multivariate analysis for OS and PFS demonstrated that the biweekly regimen was the only significant factor that affected OS, and not PFS (HR=0.561, p=0.049). Kaplan-Meier analysis indicated that neutropenia (grade ≥3) in the biweekly group was significantly prolonged compared to the standard group (p=0.012). However, there were no significant differences in adverse events between the two groups (p>0.999). CONCLUSION: The biweekly FTD/TPI regimen, compared to the standard regimen, should enhance both OS and PFS in patients with mCRC without escalating any adverse event.

Integration of reinforcement learning to realize functional variability of microfluidic systems.

In this article, we present a proof-of-concept for microfluidic systems with high functional variability using reinforcement learning. By mathematically defining the objective of tasks, we demonstrate that the system can autonomously learn to behave according to its objectives. We applied Q-learning to a peristaltic micropump and showed that two different tasks can be performed on the same platform: adjusting the flow rate of the pump and manipulating the position of the particles. First, we performed typical micropumping with flow rate control. In this task, the system is rewarded according to the deviation between the average flow rate generated by the micropump and the target value. Therefore, the objective of the system is to maintain the target flow rate via an operation of the pump. Next, we demonstrate the micromanipulation of a small object (microbead) on the same platform. The objective was to manipulate the microbead position to the target area, and the system was rewarded for the success of the task. These results confirmed that the system learned to control the flow rate and manipulate the microbead to any randomly chosen target position. In particular, the manipulation technique is a new technology that does not require the use of structures such as wells or weirs. Therefore, this concept not only adds flexibility to the system but also contributes to the development of novel control methods to realize highly versatile microfluidic systems.

Adoption of reinforcement learning for the intelligent control of a microfluidic peristaltic pump.

We herein report a study on the intelligent control of microfluidic systems using reinforcement learning. Integrated microvalves are utilized to realize a variety of microfluidic functional modules, such as switching of flow pass, micropumping, and micromixing. The application of artificial intelligence to control microvalves can potentially contribute to the expansion of the versatility of microfluidic systems. As a preliminary attempt toward this motivation, we investigated the application of a reinforcement learning algorithm to microperistaltic pumps. First, we assumed a Markov property for the operation of diaphragms in the microperistaltic pump. Thereafter, components of the Markov decision process were defined for adaptation to the micropump. To acquire the pumping sequence, which maximizes the flow rate, the reward was defined as the obtained flow rate in a state transition of the microvalves. The present system successfully empirically determines the optimal sequence, which considers the physical characteristics of the components of the system that the authors did not recognize. Therefore, it was proved that reinforcement learning could be applied to microperistaltic pumps and is promising for the operation of larger and more complex microsystems.

Motion Artifact Canceling PPG Heart Rate Sensor Based on an Adaptive Filter Algorithm with Variable Tap Length.

When estimating the heart rate (HR) of an exerciser by using a photoplethysmographic (PPG) sensor, the PPG output is contaminated with motion artifact (MA) induced by his motion, resulting in erroneous HR. To cancel the MA in the PPG output, we have proposed a technique based on adaptive filter algorithm using an MA sensor. On the one hand, we have so far fixed the tap length of the adaptive filter algorithm for the sake of its simple implementation, but on the other hand, we have noticed that the tap length dynamically changes according to the type of sensor wearer, the intensity of exercise and so on. Therefore, in this paper, we propose an MA canceling-PPG HR sensor system based on a serially configured adaptive filter algorithm with variable tap length. Experimental results involving 13 subjects reveal that the MA canceling technique based on the proposed serial configuration outperforms that with a conventional parallel configuration, achieving the minimum root mean square error of 9.97 beats per minute with much less computational complexity.

Detection Accuracy of Soccer Players in Aerial Images Captured from Several Viewpoints.

In the fields of professional and amateur sports, players' health, physical and physiological conditions during exercise should be properly monitored and managed. The authors of this paper previously proposed a real-time vital-sign monitoring system for players using a wireless multi-hop sensor network that transmits their vital data. However, existing routing schemes based on the received signal strength indicator or global positioning system do not work well, because of the high speeds and the density of sensor nodes attached to players. To solve this problem, we proposed a novel scheme, image-assisted routing (IAR), which estimates the locations of sensor nodes using images captured from cameras mounted on unmanned aerial vehicles. However, it is not clear where the best viewpoints are for aerial player detection. In this study, the authors investigated detection accuracy from several viewpoints using an aerial-image dataset generated with computer graphics. Experimental results show that the detection accuracy was best when the viewpoints were slightly distant from just above the center of the field. In the best case, the detection accuracy was very good: 0.005524 miss rate at 0.01 false positive-per-image. These results are informative for player detection using aerial images and can facilitate to realize IAR.

Effect of Position and Fastening Belt Pressure on the Accuracy of PPG-Based Heart Rate Sensor.

Photoplethysmography (PPG) is simple, non-invasive and unobtrusive, so it has been commonly used for heart rate (HR) sensing during exercise. PPG-based HR sensor can be applied for almost any part of human body where there is an artery close to the sensor, just by stabilizing it on the skin surface with belt. However, in order to make the HR sensor stable even during vigorous exercise, it requires a high fastening belt pressure, which results in discomfort for the sensor wearer. In this paper, we investigate the relationship between fastening belt pressure and accuracy for PPG-based HR sensors put on two positions such as forearm and wrist. First of all, we conducted a preliminary experiment using 10 subjects to associate fastening belt pressure (from 10hPa to 90hPa) to human comfort or discomfort (loose, moderate, tight, and very tight). Then, we conducted an experiment to measure HR for 10 subjects during exercise, changing the belt pressure and exercise intensity. Experimental results reveal that the forearm position gives higher accuracy for HR sensing than the wrist position, however, exercise severely introduces motion artifact (MA) even for the for earm position. Therefore, if we want to achieve higher accuracy during exercise with moderate fastening belt pressure, a technique to cancel MA is required even for forearm-type PPG-based HR sensors.

Hemoglobin Value Is the Most Important Factor in the Development of Hand-Foot Syndrome under the Capecitabine Regimen.

BACKGROUND: Hand-foot syndrome (HFS) is a common side effect that has a high occurrence rate with capecitabine (Cape) chemotherapy. However, little is known about the risk factors of developing HFS under the Cape regimen. Our aim was to examine these risk factors. METHODS: A univariate analysis was used to determine the risk factors associated with developing HFS, and we calculated the effect sizes between the patients who developed HFS compared to those who did not. RESULTS: Of the 52 patients enrolled in our research, 24 (46.2%) developed HFS. This group was significantly associated with hemoglobin (Hb) values (p < 0.001), and the effect size (1.21) was more than moderate. The receiver operating characteristic curve analysis confirmed 12 mg/dl Hb as the best diagnostic cut-off value for developing HFS. The sensitivity and specificity were 75.5 and 88.2%, respectively. Patients who had Hb values of 12 or below who developed HFS had longer median times without HFS compared to patients with high Hb values (115 vs. 75 days, p = 0.30, hazard ratio = 1.42, 95% CI 0.73-2.76) and a greater area under the Kaplan-Meier curves (p < 0.05). CONCLUSION: This research suggests that the Hb value is an important factor for developing HFS.

VO2 estimation using 6-axis motion sensor with sports activity classification.

In this paper, we focus on oxygen consumption (VO2) estimation using 6-axis motion sensor (3-axis accelerometer and 3-axis gyroscope) for people playing sports with diverse intensities. The VO2 estimated with a small motion sensor can be used to calculate the energy expenditure, however, its accuracy depends on the intensities of various types of activities. In order to achieve high accuracy over a wide range of intensities, we employ an estimation framework that first classifies activities with a simple machine-learning based classification algorithm. We prepare different coefficients of linear regression model for different types of activities, which are determined with training data obtained by experiments. The best-suited model is used for each type of activity when VO2 is estimated. The accuracy of the employed framework depends on the trade-off between the degradation due to classification errors and improvement brought by applying separate, optimum model to VO2 estimation. Taking this trade-off into account, we evaluate the accuracy of the employed estimation framework by using a set of experimental data consisting of VO2 and motion data of people with a wide range of intensities of exercises, which were measured by a VO2 meter and motion sensor, respectively. Our numerical results show that the employed framework can improve the estimation accuracy in comparison to a reference method that uses a common regression model for all types of activities.

Applying neural network to VO2 estimation using 6-axis motion sensing data.

This paper focuses on oxygen consumption (VO2) estimation using 6-axis motion data (3-axis acceleration and 3-axis angular velocity) that are obtained from small motion sensors attached to people playing sports with different intensities. In order to achieve high estimation accuracy over a wide range of intensities of exercises, we apply neural network that is trained by experimental data consisting of the measured VO2 and motion sensing data of people with a wide range of intensities of exercises. We first investigate the gain brought by applying neural network by comparing its accuracy with an approach based on the linear regression model. Then, we analyze how much improvement the information on angular velocity can bring as compared with the estimation with the acceleration data alone. Our numerical results show that the employed framework exploiting neural network can improve the estimation accuracy in comparison to the linear regression model and the exploitation of information on the angular velocity plays an important role to improve the accuracy over higher intensities of exercises.

Motion artifact cancellation and outlier rejection for clip-type ppg-based heart rate sensor.

Heart rate sensing can be used to not only understand exercise intensity but also detect life-critical condition during sports activities. To reduce stress during exercise and attach heart rate sensor easily, we developed a clip-type photoplethysmography (PPG)-based heart rate sensor. The sensor can be attached just by hanging it to the waist part of undershorts, and furthermore, it employs the motion artifact (MA) cancellation technique. However, due to its low contact pressure, sudden jumps and drops, which are called "outliers," are often observed in the sensed heart rate, so we also developed a simple outlier rejection technique. By an experiment using five male subjects (4 sets per subject), we confirmed the MA cancellation and outlier rejection capabilities.

Real-time sensing, transmission and analysis for vital signs of persons during exercises.

Real-time monitoring of vital signs from persons during exercises is useful from the medical, healthcare and sports physiological points of view. In professional team sports, physical trainers or technical coaches want to manage the physical conditions of athletes during exercise training in the grounds, on the other hand, in elementary and junior high schools, teachers want to take care of schoolchildren during physical training. In realization of the vital signs monitoring, there are three technical problems to be solved. The first is how to accurately sense vital signs, the second is how to reliably transmit them by wireless, and the third is how to identify factors effective for disease screening, injury prevention, performance analysis and talent identification. In this paper, we present the necessity of real-time monitoring of vital signs from persons during exercises, introduce solutions for the problems which we have so far worked out, and point out remaining technical problems.

Cancellation of motion artifact induced by exercise for PPG-based heart rate sensing.

Heart rate (HR) sensing during exercise is essential for medical, healthcare and sport physiological purposes. Photo-Plethysmo-Graphy (PPG) is a simple and non-invasive technique for HR sensing, but it is highly sensitive to motion artifact. This paper proposes a cancellation technique of motion artifact in PPG-based HR sensing for a man during exercise. The canceller is equipped with two sensors; one is a normal PPG sensor where an LED/Photo-Detector (PD) contacts the skin to detect Blood Volume Pulse (BVP) (+motion artifact) and the other is a motion artifact sensor where an LED/PD does not contact the skin to detect only motion artifact. Experimental results show that the proposed technique, which is implemented in adaptive algorithms, can sense HR correctly by cancelling motion artifact induced by exercises such as running and jumping.

Application of the real-time Retinex image enhancement for endoscopic images.

This paper presents a real-time image enhancement technique for gastric endoscopy, which is based on the variational approach of the Retinex theory. In order to efficiently reduce the computational cost required for image enhancement, processing layers and repeat counts of iterations are determined in accordance with software evaluation result, and as for processing architecture, the pipelining architecture can handle high resolution pictures in real-time. To show its potential, performance comparison between with and without the proposed image enhancement technique is shown using several video images obtained by endoscopy for different parts of digestive organ.

Neoadjuvant epirubicin/docetaxel (ET) concomitant chemotherapy for primary breast cancer with tumor diameter >=3.1 cm: results of the Kyushu ET therapy phase II trial.

AIM: Neoadjuvant epirubicin/docetaxel (ET) combination chemotherapy was administered to breast cancer patients in order to investigate their clinical and pathological response. Moreover, the breast-conserving surgery (BCS) rate, disease-free (DFS) and overall survival (OS), safety profile and the correlation of biological markers were investigated. PATIENTS AND METHODS: Out of the 46 enrolled patients, 45 patients were analyzed for clinical response, and 40 patients were examined for pathological response. Estrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor receptor type2 (HER2) expression were examined immunohistologically. RESULTS: The median tumor size was 4.5 cm in diameter. Complete (CR) and partial responses were seen in 3 and 30 patients, respectively. A pathological CR was achieved in 4 patients and correlated with ER and PgR negativity. Moreover, BCS was performed on 16 patients. The 5-year cumulative DFS was 60.7% and OS was 91.8%. CONCLUSION: ET therapy is clinically effective with a pathological CR rate of 10% for patients with a large tumor, and should be considered as a neoadjuvant treatment option.

[Docetaxel in combination with epirubicin as the first-line chemotherapy for advanced and recurrent breast cancer: a multicenter phase II study].

This study examined the efficacy and tolerability of docetaxel(DOC)in combination with epirubicin(EPI)as the first-line treatment for patients with advanced and recurrent breast cancer. A total of 56 female patients with metastatic breast cancer not previously treated for metastatic disease received DOC(60mg/m²)and EPI(60mg/m2)on day 1 every 3 weeks. The patient characteristics included a median age of 53 years. Advanced disease was present in 86% of patients, and recurrent disease was found in 14%; 3 or more metastatic sites had been diagnosed in 38% of patients, and 59% patients were ER+. The median number of courses administered was 6. The median dose intensity was 18. 7mg/m²week for DOC and EPI, and the relative dose intensities were 93. 5%and 93. 3%, respectively. The clinical responses included a complete response in 5%, a partial response in 54%, and stable disease in 33% of patients, with a disease control rate of 92%. The progression-free survival was 78. 3%, and the overall survival was 91. 9% at 1 year. Grade 3/4 toxicities included neutropenia in 82%, leukopenia in 71%, febrile neutropenia in 16%, anorexia in 9%, and anemia in 7%of the patients. Neither congestive heart failure nor toxic death occurred. The D and E combination with doses of 60mg/m2 is an active and generally well-tolerated regimen that can be used as first-line chemotherapy for patients with metastatic breast cancer.

Development of a triage engine enabling behavior recognition and lethal arrhythmia detection for remote health care system.

For ubiquitous health care systems which continuously monitor a person's vital signs such as electrocardiogram (ECG), body surface temperature and three-dimensional (3D) acceleration by wireless, it is important to accurately detect the occurrence of an abnormal event in the data and immediately inform a medical doctor of its detail. In this paper, we introduce a remote health care system, which is composed of a wireless vital sensor, multiple receivers and a triage engine installed in a desktop personal computer (PC). The middleware installed in the receiver, which was developed in C++, supports reliable data handling of vital data to the ethernet port. On the other hand, the human interface of the triage engine, which was developed in JAVA, shows graphics on his/her ECG data, 3D acceleration data, body surface temperature data and behavior status in the display of the desktop PC and sends an urgent e-mail containing the display data to a pre-registered medical doctor when it detects the occurrence of an abnormal event. In the triage engine, the lethal arrhythmia detection algorithm based on short time Fourier transform (STFT) analysis can achieve 100 % sensitivity and 99.99 % specificity, and the behavior recognition algorithm based on the combination of the nearest neighbor method and the Naive Bayes method can achieve more than 71 % classification accuracy.

Clinical tests and evaluations of a wireless ECG sensor for realization of ubiquitous health care systems.

This paper introduces the concept of an online medical diagnosis system for ubiquitous health care using a wireless ECG sensor. To confirm the feasibility ofthe system, we conducted clinical tests by 67 subjects with a wireless ECG sensor and a Holter ECG monitor simultaneously for comparison purpose. We made five types of evaluations such as analyses on data loss rate, burst data loss length, ECG waveforms comparison, normalized cross-correlation and heart rate variability (HRV) by RR50. The results show that, as long as the sensed data are successfully received at a receiver, the wireless ECG sensor has a comparable performance with the Holter ECG monitor.

A receiver diversity technique for ensuring high reliability of wireless vital data gathering in hospital rooms.

Sensing and wireless technologies have made remarkable advance recently, so wireless vital sensors for medical use, which are light-weight but accurate, have been commercially available. However, because of the low reliability of the wireless data transmission, sensed vital data are often lost in the wireless channel and this is a fatal drawback of the devices for continuous monitoring of patients in hospitals. This paper investigates the effect of using multiple receivers (receiver diversity technique) on the improvement of data loss rate for wireless vital data gathering. Experiments with a wireless vital sensor in hospital rooms reveal that putting receivers to higher positions such as ceiling is advantageous and the use of three receivers can sufficiently improve the data loss rate as compared with the use of a single receiver.

[A case of N3 gastric cancer successfully treated by TS-1 followed by curative resection].

We report a case of N 3 gastric cancer successfully treated by TS-1 followed by curative resection. The patient was a 64-year-old male. Gastrointestinal endoscopic examination showed advanced gastric cancer. Examination by computed tomography revealed gastric cancer and swollen para-aortic lymph nodes. This patient was treated by neoadjuvant chemotherapy with oral administration of TS-1 (120 mg/day, day 1-28 with 2 weeks rest). After 3 courses of TS-1, the primary lesion and swollen lymph nodes were remarkably reduced. This chemotherapy enabled pancreatoduodenectomy with D 3 lymph node dissection in curative resection. The pathological diagnosis was por, pT 2, pMP and pap, pT 1, pSM 2, pPM(-), pDM(-), pN 1, pStage II and curability A. This neoadjuvant chemotherapy regimen seems to be an effective and promising therapy for patients with advanced gastric cancer.