[Evaluation of physical activity using smartphones and wearable devices in healthcare: Current situation and future perspectives].

Abstract　With the growing popularity of mobile health (mHealth) devices, including smartphones and wearable devices, information and communications technology has gained high importance in healthcare settings. This study aimed to summarize the current trends in physical activity research wherein mHealth devices are used and provide perspectives for future research. Until recently, questionnaire surveys were primarily used to evaluate physical activity. While questionnaire surveys are effective for subjective evaluation, the use of mHealth devices enables large-scale, real-time, objective evaluation of physical activity. In addition, mHealth devices automatically collect and aggregate data. This allows researchers to perform retrospective analysis of a wide range of indicators of physical activity and health. Particularly, the use of smartphones is highly likely to contribute to large-scale monitoring and health interventions because of their ubiquity. Even though there are fewer users of wearable devices (wrist-worn devices) than those of smartphones, using wearable devices allows for the evaluation of 24-hour movement patterns. The use of wearable devices helps perform further precise analysis that focuses not only on the total amount of physical activity but also on the quality, including measures of intensity, duration, frequency, type, and time. Moreover, some wrist-worn devices measure physiological information such as heart rate and may also provide location information. Combining such data with information from an accelerometer associated with a device may allow for further specific and detailed evaluation of physical activity. The validity of physical activity assessment using major mHealth devices has been confirmed in several studies and is comparable to that of pedometers and accelerometers developed for research purposes. Evaluation of physical activity using mHealth devices involves issues related to the representativeness of the target population and continuity of data, as well as the need for ethical considerations based on privacy policies. While mHealth devices may be used by individuals as a health management tool, it is also expected that the evaluation of physical activity using mHealth devices will be performed in various settings such as epidemiological and clinical studies on physical activity, as well as community services wherein indicators of physical activity are used.

A strategy to account for noise in the X-variable to reduce underestimation in Logan graphical analysis for quantifying receptor density in positron emission tomography.

BACKGROUND: The Logan graphical analysis (LGA) algorithm is widely used to quantify receptor density for parametric imaging in positron emission tomography (PET). Estimating receptor density, in terms of the non-displaceable binding potential (BPND), from the LGA using the ordinary least-squares (OLS) method has been found to be negatively biased owing to noise in PET data. This is because OLS does not consider errors in the X-variable (predictor variable). Existing bias reduction methods can either only reduce the bias slightly or reduce the bias accompanied by increased variation in the estimates. In this study, we addressed the bias reduction problem by applying a different regression method. METHODS: We employed least-squares cubic (LSC) linear regression, which accounts for errors in both variables as well as the correlation of these errors. Noise-free PET data were simulated, for 11C-carfentanil kinetics, with known BPND values. Statistical noise was added to these data and the BPNDs were re-estimated from the noisy data by three methods, conventional LGA, multilinear reference tissue model 2 (MRTM2), and LSC-based LGA; the results were compared. The three methods were also compared in terms of beta amyloid (A ß) quantification of 11C-Pittsburgh compound B brain PET data for two patients with Alzheimer's disease and differing A ß depositions. RESULTS: Amongst the three methods, for both synthetic and actual data, LSC was the least biased, followed by MRTM2, and then the conventional LGA, which was the most biased. Variations in the LSC estimates were smaller than those in the MRTM2 estimates. LSC also required a shorter computational time than MRTM2. CONCLUSIONS: The results suggest that LSC provides a better trade-off between the bias and variability than the other two methods. In particular, LSC performed better than MRTM2 in all aspects; bias, variability, and computational time. This makes LSC a promising method for BPND parametric imaging in PET studies.

Downregulation of Plasma miR-215 in Chronic Myeloid Leukemia Patients with Successful Discontinuation of Imatinib.

Approximately 40% of chronic myeloid leukemia (CML) patients who discontinue imatinib (IM) therapy maintain undetectable minimal residual disease (UMRD) for more than one year (stopping IM (STOP-IM)). To determine a possible biomarker for STOP-IM CML, we examined plasma miRNA expression in CML patients who were able to discontinue IM. We first screened candidate miRNAs in unselected STOP-IM patients, who had sustained UMRD after discontinuing IM for more than six months, in comparison with healthy volunteers, by using a TaqMan low-density array for plasma or exosomes. Exosomal miR-215 and plasma miR-215 were downregulated in the STOP-IM group compared to the control, indicating that the biological relevance of the plasma miR-215 level is equivalent to that of the exosomal level. Next, we performed real-time quantitative RT-PCR in 20 STOP-IM patients, 32 patients with UMRD on continued IM therapy (IM group) and 28 healthy volunteers. The plasma miRNA-215 level was significantly downregulated in the STOP-IM group (p < 0.0001); we determined the cut-off level and divided the IM group patients into two groups according to whether the plasma miR-215 was downregulated or not. The IM group patients with a low plasma miR-215 level had a significantly higher total IM intake, compared to the patients with elevated miR-215 levels (p = 0.0229). Functional annotation of miR-215 target genes estimated by the Database for Annotation, Visualization and Integrated Discovery (DAVID) bioinformatic tools involved cell cycle, mitosis, DNA repair and cell cycle checkpoint. Our study suggests a possible role of miR-215 in successful IM discontinuation.

Development of a compact wireless Laplacian electrode module for electromyograms and its human interface applications.

In this study, we developed a compact wireless Laplacian electrode module for electromyograms (EMGs). One of the advantages of the Laplacian electrode configuration is that EMGs obtained with it are expected to be sensitive to the firing of the muscle directly beneath the measurement site. The performance of the developed electrode module was investigated in two human interface applications: character-input interface and detection of finger movement during finger Braille typing. In the former application, the electrode module was combined with an EMG-mouse click converter circuit. In the latter, four electrode modules were used for detection of finger movements during finger Braille typing. Investigation on the character-input interface indicated that characters could be input stably by contraction of (a) the masseter, (b) trapezius, (c) anterior tibialis and (d) flexor carpi ulnaris muscles. This wide applicability is desirable when the interface is applied to persons with physical disabilities because the disability differs one to another. The investigation also demonstrated that the electrode module can work properly without any skin preparation. Finger movement detection experiments showed that each finger movement was more clearly detectable when comparing to EMGs recorded with conventional electrodes, suggesting that the Laplacian electrode module is more suitable for detecting the timing of finger movement during typing. This could be because the Laplacian configuration enables us to record EMGs just beneath the electrode. These results demonstrate the advantages of the Laplacian electrode module.

Systems analysis of inflammatory bowel disease based on comprehensive gene information.

BACKGROUND: The rise of systems biology and availability of highly curated gene and molecular information resources has promoted a comprehensive approach to study disease as the cumulative deleterious function of a collection of individual genes and networks of molecules acting in concert. These "human disease networks" (HDN) have revealed novel candidate genes and pharmaceutical targets for many diseases and identified fundamental HDN features conserved across diseases. A network-based analysis is particularly vital for a study on polygenic diseases where many interactions between molecules should be simultaneously examined and elucidated. We employ a new knowledge driven HDN gene and molecular database systems approach to analyze Inflammatory Bowel Disease (IBD), whose pathogenesis remains largely unknown. METHODS AND RESULTS: Based on drug indications for IBD, we determined sibling diseases of mild and severe states of IBD. Approximately 1,000 genes associated with the sibling diseases were retrieved from four databases. After ranking the genes by the frequency of records in the databases, we obtained 250 and 253 genes highly associated with the mild and severe IBD states, respectively. We then calculated functional similarities of these genes with known drug targets and examined and presented their interactions as PPI networks. CONCLUSIONS: The results demonstrate that this knowledge-based systems approach, predicated on functionally similar genes important to sibling diseases is an effective method to identify important components of the IBD human disease network. Our approach elucidates a previously unknown biological distinction between mild and severe IBD states.

Application of correlated component analysis to dynamic PET time-activity curves denoising.

Positron emission tomography (PET) is a physiological, non-invasive imaging technique, which forms an essential part of nuclear medicine. The data obtained in a PET scan represent the concentration of an administered radiotracer in tissues over time. Quantitative analysis of PET data makes possible the assessments of in-vivo physiological processes. The Logan graphical analysis (LGA) is one of the methods that are used for quantitative analysis of PET data. LGA transforms PET data into a simple linear relationship. The slope of the LGA linear relationship is a physiological quantity denoting receptor availability. This quantity is termed distribution volume ratio (DVR). LGA-based estimates of the DVR are negatively affected by the noise in PET data -leading to the DVR being underestimated. A number of approaches proposed to address this issue have been observed to reduce the bias at the cost precision. An alternative regression method, least-squares cubic (LSC), was recently applied to estimate the DVR in order to reduce the bias. LSC was observed to reduce the bias in the LGA-based estimates. However, slight increases were also observed in the variance of the LSC-based estimates. This calls for methods to act against the variance in the LSC-based estimates. In this study, an alternative method is applied for tTAC denoising. This method is referred to as correlated component analysis (CorrCA). CorrCA transform the data by searching for dimensions of maximum correlation. This technique is closely related to other well-known methods such as principal component analysis and independent component analysis. In this study, the data were denoised by CorrCA (to act against the variance in the estimate) and the DVR was estimated by LSC, which provides for minimal bias. The resulting method LSC-CorrCA, gave less-biased estimated with increased precision. This was observed for both simulation results as well as for clinical data, both for 11C Pittsburgh compound B. Simulation data revealed reduced variances in LCS-CorrCA-based estimates, and the clinical data showed improved contrast between gray and white matter regions.Clinical Relevance-Improved DVR estimates would ease the interpretation of medical images, which will in turn positively influence the clinical processes, from diagnosis to treatment and follow-ups.

Improving contrast between gray and white matter of Logan graphical analysis' parametric images in positron emission tomography through least-squares cubic regression and principal component analysis.

Logan graphical analysis (LGA) is a method forin vivoquantification of tracer kinetics in positron emission tomography (PET). The shortcoming of LGA is the presence of a negative bias in the estimated parameters for noisy data. Various approaches have been proposed to address this issue. We recently applied an alternative regression method called least-squares cubic (LSC), which considers the errors in both the predictor and response variables to estimate the LGA slope. LSC reduced the bias in non-displaceable binding potential estimates while causing slight increases in the variance. In this study, we combined LSC with a principal component analysis (PCA) denoising technique to counteract the effects of variance on parametric image quality, which was assessed in terms of the contrast between gray and white matter. Tissue time-activity curves were denoised through PCA, prior to estimating the regression parameters using LSC. We refer to this approach as LSC-PCA. LSC-PCA was assessed against OLS-PCA (PCA with ordinary least-squares (OLS)), LSC, and conventional OLS-based LGA. Comparisons were made for simulated11C-carfentanil and11C Pittsburgh compound B (11C-PiB) data, and clinical11C-PiB PET images. PCA-based methods were compared over a range of principal components, varied by the percentage variance they account for in the data. The results showed reduced variances in distribution volume ratio estimates in the simulations for LSC-PCA compared to LSC, and lower bias compared to OLS-PCA and OLS. Contrasts were not significantly improved in clinical data, but they showed a significant improvement in simulation data -indicating a potential advantage of LSC-PCA over OLS-PCA. The effects of bias reintroduction when many principal components are used were also observed in OLS-PCA clinical images. We therefore encourage the use of LSC-PCA. LSC-PCA can allow the use of many principal components with minimal risk of bias, thereby strengthening the interpretation of PET parametric images.

Changes in Autonomic Nervous System and Axillary Temperature Caused by Electric Potential Therapy.

This paper describes two experiments conducted to investigate changes in the autonomic nervous system and axillary temperature caused by electric potential therapy. The former was investigated using a frequency analysis of successive heartbeats (RR intervals) and cortisol in saliva. The experimental results on the RR intervals suggest no significant change in the autonomic nervous system, but those on the saliva cortisol indicate a change in the system during the therapy. The axillary temperature showed a significant increase. The results on the autonomic nervous system seem inconsistent, and these results as well as future directions were discussed.

Machine Learning Approach for Predicting New Uses of Existing Drugs and Evaluation of Their Reliabilities.

In this chapter, a new method to evaluate the reliability of predicting new uses of existing drugs was proposed. The prediction was performed with a support vector machine (SVM) using various data. Because the reliability of prediction could not be evaluated based on the output of an SVM, which was binary, the proposed method evaluated the reliability as a product of a distance from the separating hyperplane of the SVM and a similarity between the disease targeted by the drug and a candidate disease. A validation using real data revealed that the performance of the proposed method was promising.

Stability of the human upright stance depending on the frequency of external disturbances.

During an upright stance of humans, it is usually assumed that a stiffer ankle joint contributes to stabilize the stance. To show that under certain conditions a stiffer ankle joint can reduce the stability, the frequency responses of the moment and the angle of the ankle joint against external disturbances caused by random horizontal translations of the support surface were evaluated in ten healthy adult subjects by varying the difficulty of the task at four levels. When it was difficult to keep the upright stance, the subject tended to make the ankle joint stiffer. The transfer function relating the external disturbance moment to the ankle joint moment showed a larger gain in the high frequency range (>0.3 Hz) compared with the gains obtained under easier conditions. A simulation analysis based on a simple inverted pendulum model also reproduced this tendency. These results indicate that the stiffer ankle joint and the resulting higher ankle moment for high frequency external disturbances enhance the possibility that the center of pressure exceeds the limit arising from the size of the feet and can make the upright stance unstable.

Information Encoding Methods for a Balance Assist Device Using Vibrotactile Feedback.

This study investigates the applicability of information encoding methods for a balance assist device using vibrotactile feedback. In the device, two motors were employed to provide information on the model's sway angle in each of the forward and backward directions. In the experiment involving ten healthy volunteers, two encoding modes with different vibration patterns were compared using an equivalent body model. The influence of proficiency level was also investigated. The results indicated that a simple encoding method outperformed a complex one even after the proficiency level was improved. Further analyses on the input and output of the model indicated the necessity of a time domain signal for encoding feedback information with the complex encoding methodology.

Sensory stimulation triggers spindles during sleep stage 2.

STUDY OBJECTIVES: Toward understanding the function of sleep spindle, we examined whether sensory stimulation triggers sleep spindles. PARTICIPANTS: Eleven normal subjects participated in the experiments. INTERVENTION: The subjects had a nap in the afternoon, and sensory stimulation was applied during sleep stage 2. MEASUREMENTS: 21-channel EEG was recorded during the 2-3 hour experiment carried out between 13:00 and 16:00. Somatosensory, auditory, or visual stimulation was performed over a 5-minute period during stage 2. The frequency and duration of spindles were compared in 2 different segments of 5 minutes, with and without sensory stimulation. The latency from the onset of a sensory stimulus to the succeeding spindle was also analyzed. To estimate the active brain regions during a spindle, the EEG recordings were modeled with a single equivalent moving dipole (SEMD) model. RESULTS: In the period with stimulation, spindle frequency and duration increased compared with the period without stimulation. Statistical tests revealed that with stimulation, the interval between 2 consecutive spindles was significantly shorter (p < 0.05, regardless of the modality) and that the duration of the spindles was significantly longer with stimulation (p < 0.05, regardless of the modality). The latency was approximately 2 s. During a spindle after somatosensory stimulation brain activities were observed near the somatosensory area, while with auditory stimulation active regions were observed near the auditory cortex. CONCLUSIONS: A sensory stimulus appeared to trigger a sleep spindle during sleep stage 2. SEMD trajectories suggest that active brain regions during spindle are different according to the modality of the preceding stimulus.

Range of motion measurement of an artificial hip joint using CT images.

Total hip arthroplasty (THA) is one of the most effective treatments for osteoarthritis and rheumatoid arthritis. Dislocation of the femoral head from the acetabular socket is a major problem of THA. To prevent dislocation, it is important to know the range of motion (ROM) after THA. Although various studies on the ROM were carried out, there exist only a few reports on ROM evaluation in individual patients. This is because in clinical cases, bone-to-bone and bone-to-component contacts must be considered besides the impingement of components. In this study, a new method for evaluating ROM of internal/external rotation, which takes into account all combinations of contacts between the bones and components, was proposed. A computer simulation demonstrated that the RMS error of the proposed method was approximately 3 degrees . The method was applied to 33 THAs under various conditions of flexion and adduction angles. The method was able to detect any type of impingement. The evaluated ROM was in good agreement with that measured during the THA operation (correlation coefficient = 0.91).

Cross-coupling in a body-translating reaction: interaural optokinetic stimulation reflects a gravitational cue.

CONCLUSION: The velocity storage integrator does not play a dominant role in the postural response to vertical visual cues; more likely, retinal slip provides the main driving force. By contrast, sideways eye movement can drive the velocity storage integrator and preserve a gravitational cue, which would be observed as a cross-coupling effect on the postural response. OBJECTIVES: To investigate the mechanism by which optokinetic stimulation causes the body to translate and to determine whether the optokinetic information is accompanied by a gravitational cue, which would appear as a cross-coupling effect. MATERIALS AND METHODS: Directionally diverse optokinetic stimuli were presented to seven healthy subjects, with and without a fixation target, and the body-translation of the subjects was recorded. RESULTS: Horizontal optokinetic stimulation with a fixation target caused the body to translate in the same direction as the optic flow. Upward or downward vertical optokinetic stimulation caused the body to translate backward or forward, respectively, only when a fixation target was present. When the subject's interaural axis was parallel to the optokinetic flow, diagonal optokinetic stimulation in the absence of a fixation target elicited responses in the pitch plane similar to those elicited by vertical stimulation in the presence of a fixation target.

Lower expression of genes near microRNA in C. elegans germline.

BACKGROUND: MicroRNAs (miRNAs) are recently discovered short non-protein-coding RNA molecules. miRNAs are increasingly implicated in tissue-specific transcriptional control and particularly in development. Because there is mounting evidence for the localized component of transcriptional control, we investigated if there is a distance-dependent effect of miRNA. RESULTS: We analyzed gene expression levels around the 84 of 113 know miRNAs for which there are nearby gene that were measured in the data in two independent C. elegans expression data sets. The expression levels are lower for genes in the vicinity of 59 of 84 (71%) miRNAs as compared to genes far from such miRNAs. Analysis of the genes with lower expression in proximity to the miRNAs reveals increased frequency matching of the 7 nucleotide "seed"s of these miRNAs. CONCLUSION: We found decreased messenger RNA (mRNA) abundance, localized within a 10 kb of chromosomal distance of some miRNAs, in C. elegans germline. The increased frequency of seed matching near miRNA can explain, in part, the localized effects.

Applicability of the single equivalent moving dipole model in an infinite homogeneous medium to identify cardiac electrical sources: a computer simulation study in a realistic anatomic geometry torso model.

We have previously proposed an inverse algorithm for fitting potentials due to an arbitrary bio-electrical source to a single equivalent moving dipole (SEMD) model. The algorithm achieves fast identification of the SEMD parameters by employing a SEMD model embedded in an infinite homogeneous volume conductor. However, this may lead to systematic error in the identification of the SEMD parameters. In this paper, we investigate the accuracy of the algorithm in a realistic anatomic geometry torso model (forward problem). Specifically, we investigate the effect of measurement noise, dipole position and electrode configuration in the accuracy of the algorithm. The boundary element method was used to calculate the forward potential distribution at multiple electrode positions on the body surface due to a point dipole in the heart. We have found that the position and not the number of electrodes as well as the site of the origin of the arrhythmia in the heart have a significant effect on the accuracy of the inverse algorithm, while the measurement noise does not. Finally, we have shown that the inverse algorithm preserves the topology of the source distribution in the heart, thus potentially allowing the cardiac electrophysiologist to efficiently and accurately guide the tip of the catheter to the ablation site.

Inter-species differences of co-expression of neighboring genes in eukaryotic genomes.

BACKGROUND: There is increasing evidence that gene order within the eukaryotic genome is not random. In yeast and worm, adjacent or neighboring genes tend to be co-expressed. Clustering of co-expressed genes has been found in humans, worm and fruit flies. However, in mice and rats, an effect of chromosomal distance (CD) on co-expression has not been investigated yet. Also, no cross-species comparison has been made so far. We analyzed the effect of CD as well as normalized distance (ND) using expression data in six eukaryotic species: yeast, fruit fly, worm, rat, mouse and human. RESULTS: We analyzed 24 sets of expression data from the six species. Highly co-expressed pairs were sorted into bins of equal sized intervals of CD, and a co-expression rate (CoER) in each bin was calculated. In all datasets, a higher CoER was obtained in a short CD range than a long distance range. These results show that across all studied species, there was a consistent effect of CD on co-expression. However, the results using the ND show more diversity. Intra- and inter-species comparisons of CoER reveal that there are significant differences in the co-expression rates of neighboring genes among the species. A pair-wise BLAST analysis finds 8-30 % of the highly co-expressed pairs are duplicated genes. CONCLUSION: We confirmed that in the six eukaryotic species, there was a consistent tendency that neighboring genes are likely to be co-expressed. Results of pair-wised BLAST indicate a significant effect of non-duplicated pairs on co-expression. A comparison of CD and ND suggests the dominant effect of CD.

Contribution of the vestibular apparatus to postural control when rising from a chair.

OBJECTIVE: The everyday act of rising from a chair is known to require the combined angular control of a number of the body's joints, especially those within the pitch plane. Precisely how this control is exerted, however, remains controversial. The aim of this study was to obtain a better understanding of the contribution made by the vestibular apparatus to postural control of the body and head when an individual rises from a chair. MATERIAL AND METHODS: A total of 24 healthy controls and 38 patients with varying degrees of vestibular dysfunction were examined. Electromagnetic motion sensors were used to analyze the angular control of the head and body as subjects rose from a chair with their eyes open or closed. RESULTS: We found that unilateral vestibular dysfunction caused fixation of the head with respect to the body, resulting in a loss of spatial stability of the head which was not compensated for by visual input. Visual input did appear to compensate for bilateral vestibular loss, enabling patients with bilateral vestibular apparatus impairment or central disorders to fix the position of their head in space. CONCLUSION: The act of rising from a chair is normally controlled by vestibular and proprioceptive input; the head is aligned according to the gravitational reference so as to obtain stable visual information. In patients with unilateral vestibular hypofunction, posture is still controlled by these two inputs, although the ability to align the head is diminished. In patients with bilateral vestibular hypofunction or a central disorder, head alignment is maintained using visual input, although it may not be the sole or predominant stabilizing force.

Time course analysis of angular control of the body and head while rising from a chair.

OBJECTIVE: To use time course information to improve understanding of the vestibular contribution to postural control as one rises from a chair. MATERIAL AND METHODS: A total of 24 healthy controls and 42 patients with varying degrees of vestibular dysfunction were studied. The time course of the angular motion of the body and head when rising from a chair with eyes open and closed was evaluated. The delay between the onset of the motions of the body and head was compared between subject groups. We also investigated transition points from forward lean of the body to backward reversion and from backward tilt of the head to forward reversion. RESULTS: With regard to the onset of chair rise, we found a significant difference in the delay between head and body motion between healthy controls and subjects with bilaterally impaired vestibular deficiency only when the eyes were closed. The time between the transition points of the head and body was stable between these groups. CONCLUSION: The mechanisms controlling the onset of head and body movements differ between normal subjects and those with bilateral vestibular deficits. In the latter, the loss of a reference of gravity causes a decrease in feed-forward postural control, which is compensated for by a somato-sensory feedback mechanism. Visual input seems to provide an alternative reference of gravity.

A two-step drug repositioning method based on a protein-protein interaction network of genes shared by two diseases and the similarity of drugs.

The present study proposed a two-step drug repositioning method based on a protein-protein interaction (PPI) network of two diseases and the similarity of the drugs prescribed for one of the two. In the proposed method, first, lists of disease related genes were obtained from a meta-database called Genotator. Then genes shared by a pair of diseases were sought. At the first step of the method, if a drug having its target(s) in the PPI network, the drug was deemed a repositioning candidate. Because targets of many drugs are still unknown, the similarities between the prescribed drugs for a specific disease were used to infer repositioning candidates at the second step. As a first attempt, we applied the proposed method to four different types of diseases: hypertension, diabetes mellitus, Crohn disease, and autism. Some repositioning candidates were found both at the first and second steps.