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Cancer metabolism is characterized by increased macromolecular syntheses through coordinated increases in energy and substrate metabolism. The observation that cancer cells produce lactate in an environment of oxygen sufficiency (aerobic glycolysis) is a central theme of cancer metabolism known as the Warburg effect. Aerobic glycolysis in cancer metabolism is accompanied by increased pentose cycle and anaplerotic activities producing energy and substrates for macromolecular synthesis. How these processes are coordinated is poorly understood. Recent advances have focused on molecular regulation of cancer metabolism by oncogenes and tumor suppressor genes which regulate numerous enzymatic steps of central glucose metabolism. In the past decade, new insights in cancer metabolism have emerged through the application of stable isotopes particularly from 13C carbon tracing. Such studies have provided new evidence for system-wide changes in cancer metabolism in response to chemotherapy. Interestingly, experiments using metabolic inhibitors on individual biochemical pathways all demonstrate similar system-wide effects on cancer metabolism as in targeted therapies. Since biochemical reactions in the Warburg effect place competing demands on available precursors, high energy phosphates and reducing equivalents, the cancer metabolic system must fulfill the condition of balance of flux (homeostasis). In this review, the functions of the pentose cycle and of the tricarboxylic acid (TCA) cycle in cancer metabolism are analyzed from the balance of flux point of view. Anticancer treatments that target molecular signaling pathways or inhibit metabolism alter the invasive or proliferative behavior of the cancer cells by their effects on the balance of flux (homeostasis) of the cancer metabolic phenotype.

Prenatally administered rosiglitazone (RGZ) is effective in enhancing lung maturity; however, its long-term safety remains unknown. This study aimed to determine the effects of prenatally administered RGZ on the metabolic phenotype of adult rats. Methods. Pregnant Sprague-Dawley rat dams were administered either placebo or RGZ at embryonic days 18 and 19. Between 12 and 20 weeks of age, the rats underwent glucose and insulin tolerance tests and de novo fatty acid synthesis assays. The lungs, liver, skeletal muscle, and fat tissue were processed by Western hybridization for peroxisome proliferator-activated receptor (PPAR)γ, adipose differentiation-related protein (ADRP), and surfactant proteins B (SPB) and C (SPC). Plasma was assayed for triglycerides, cholesterol, insulin, glucagon, and troponin-I levels. Lungs were also morphometrically analyzed. Results. Insulin and glucose challenges, de novo fatty acid synthesis, and all serum assays revealed no differences among all groups. Western hybridization for PPARγ, ADRP, SPB, and SPC in lung, liver, muscle, and fat tissue showed equal levels. Histologic analyses showed a similar number of alveoli and septal thickness in all experimental groups. Conclusions. When administered prenatally, RGZ does not affect long-term fetal programming and may be safe for enhancing fetal lung maturation.

ObjectiveIn healthy, nonobese, adolescent males and females to: (1) Determine the relationship between fitness and energy intake; (2) assess the effect of five-weeks endurance training on energy intake and food choice and (3) compare food record assessments of energy intake with doubly-labeled water (DLW) measurement of total energy expenditure (TEE).Design(1) Cross sectional analysis of fitness and food intake and (2) Prospective, randomized, controlled interventional study of endurance-type exercise training in 44 females and 44 males (age range, 15-17 y).MeasurementsPre and end interventional three day food records were successfully collected from 32 females (15 controls, 17 trained) and 39 males (19 controls, 20 trained). Fitness was assessed from cycle ergometry as peak oxygen uptake normalized both to thigh muscle mass and body weight. Thigh muscle mass was measured by magnetic resonance imaging. TEE using the DLW technique was measured in 12 females (6 controls, 6 trained) and 20 males (10 controls, 10 trained) during weeks 4-5 of the exercise training program (simultaneously with the second assessment of food records). Food record data were analyzed using the Minnesota Nutrition Data System.ResultsFitness was correlated with self reported total caloric intake in males but not females. In females, there was a significant increase in fat intake (19.8+/-9%, P < 0.05) and a significant decrease in carbohydrate intake (-9.8+/-4%) in the trained subjects. No changes were observed in the control subjects. Energy expenditure (2072+/-52 kcal/d) was significantly greater than the estimated energy intake (1520+/-112 kcal/d, P < 0.007) during the intervention in the trained, but not control, subjects. However, there was no weight change in either control or trained subjects. In males, no changes were observed in food choice in either control or trained subjects. Similar to the females, energy expenditure (2425+/-22 kcal/d) was significantly greater than the estimated energy intake (2168+/-117 kcal/d, P < 0.05) during the intervention in the trained, but not control, subjects. No weight changes were observed in either group.ConclusionsFitness is associated with increased self-reported energy intake in males but not females, while exercise training led to alterations in food selection (greater fat and reduced carbohydrate) only in females. These observations could reflect specific gender differences, or, alternatively, the generally lower levels of fitness in the females. The apparent negative energy balance without evidence for weight loss in both the trained males and females suggests a systematic under reporting of food intake during exercise programs in adolescents, and indicates the possibility that errors in self reported food intake might be greater during transitions from one level of energy expenditure to another.

ObjectivesAmerican female adolescents are at high risk of a physically inactive lifestyle that likely leads to health problems later in life. We hypothesized that a brief program of endurance exercise training in female adolescents would result in increased energy expenditure and quantifiable structural and functional adaptations.Study designForty-four high school girls (aged 15 to 17 years, none were elite athletes) enrolled in a 5-day per week anatomy class for 5 weeks and were randomly assigned to control (n = 22) and training groups. All subjects participated in a 2-hour daily teaching program. During the remaining time (2 hours), the training group members underwent endurance-type training and control group subjects participated in a computer workshop. The intervention was assessed by (1) comparison of total energy expenditure between groups with the doubly labeled water technique, (2) determination of changes in thigh muscle volume by magnetic resonance imaging, and (3) determination of changes in maximal oxygen uptake by use of respiratory gas exchange responses.ResultsTotal energy expenditure was significantly greater (15.3%) in the training group compared with the control subjects (p < 0.003). Five weeks of training led to a 4.3% +/- 1% increase in thigh muscle volume (p < 0.0002) and a 12.1% +/- 3.7% increase in maximal oxygen uptake (p < 0.004); there were no changes in the control group. The training effect was most pronounced in the least fit subjects.ConclusionsExercise training programs for female adolescents can be successfully integrated into a high school summer curriculum. Quantifiable, substantial structural and functional responses occur with relatively short periods of training. Approximately 60% of the training response was related to factors independent of muscle size per se. These data may serve to better design physical activity programs for female adolescents.

We hypothesized that whole body glucose uptake (Rd) during exercise is not related in a simple, linear manner to O2 uptake (VO2). To test this, seven healthy male subjects (age range 23-34 yr) were studied in the postabsorptive but not glycogen-depleted state. Three conditions were examined: 1) rest, 2) 40 min of constant exercise in which the work rates were carefully chosen to consist of low-intensity exercise (no elevated blood lactate, a mean of 40% maximal VO2), and 3) 40 min of high-intensity exercise (markedly elevated blood lactate, 79% maximal VO2). Gas exchange was measured breath by breath, and glucose uptake and production were measured using [6,6-2H2]glucose. Low-intensity exercise (n = 7) resulted in a small but not statistically significant increase in mean Rd [3.06 +/- 0.37 (SE) mg.min-1.kg-1] compared with resting values (2.87 +/- 0.39 mg.min-1.kg-1) despite a fourfold increase in the production of CO2 and VO2. By contrast, the high-intensity exercise Rd (n = 5, 6.98 +/- 0.67 mg.min-1.kg-1) was significantly greater than the resting value (3.03 +/- 0.56 mg.min-1.kg-1). Results of glucose production were virtually the same. Similarly, mean levels of epinephrine and norepinephrine increased significantly above resting values during high- but not low-intensity exercise. Our data demonstrate that whole body glucose dynamics and regulation during 40 min of exercise do not change in a simple linear manner with respect to metabolic rate.

Objective. The propagation speed of a shear wave, whether externally or internally induced, in biological tissues is directly linked to the tissue's stiffness. The group shear wave speed (SWS) can be estimated using a class of time-of-flight (TOF) methods in the time-domain or phase speed-based methods in the frequency domain. However, these methods suffer from biased estimations or time-consuming computations, and they are especially prone to wave distortions in in vivo cases. In this work, we present a parameter-free, robust, and efficient group SWS estimation method coined as Fourier energy spectrum centroid (FESC). Approach. The proposed FESC method is based on the center of mass inω-kspace. It was evaluated on data from computer simulations with additive Gaussian noise, a commercial elasticity phantom, an ex vivo pig liver, and in vivo biceps brachii muscles of three young healthy male subjects. The FESC method was compared with two 2D frequency-domain methods: Max-fre, which considers phase SWS at the peak of k -space, and Fre-regre, which applies linear regression of phase SWS within a fixed bandwidth. Two additional benchmarks included time-domain methods based on cross-correlation (X-Corr) and radon sum transformation (RD). Main results. Statistical results showed that our FESC method and the RD method had comparable accuracy and robustness, outperforming the other benchmark methods. In the simulation and phantom studies, when the signal-to-noise ratio was higher than 25 dB, our FESC showed higher accuracy than RD. In the in vivo study, our FESC method had better repeatability than RD. Furthermore, the proposed FESC method was 100 times faster than the runner-up method, X-Corr, and 3,000 times faster than the least efficient method, RD. Significance. All results indicated that our proposed Fourier-based method shows promise in reliably and efficiently providing reference values for group SWS in homogeneous bulk media., (Creative Commons Attribution license.)

Objective: This study aimed to validate the ultrasound speckle tracking (UST) algorithm, determine the optimal probe location by comparing normalized cross-correlation (NCC) values of muscle displacement at two locations (proximal vs. middle) of the biceps femoris long head (BFlh) using the UST, and investigate the effects of Nordic hamstring curl exercise (NHE) training on BFlh displacement., Methods: UST efficacy was verified with ex vivo uniaxial testing of porcine leg muscles. Ten participants (mean age 23.4 y) were recruited for comparison of NCC values between the proximal and middle BFlh during maximal knee flexor eccentric contraction using an ultrasound device and isokinetic dynamometer. Using the above devices, electromyography and shear wave elastography, the effects of an 8-wk NHE program on the morphomechanical profiles, displacement and activation of the middle BFlh and eccentric torque of the knee flexor were investigated in 20 males (mean age 23.5 y)., Results: The validity of UST was confirmed by comparing UST and ex vivo test results (r = 0.99). The NCC values of the middle BFlh were greater than those of the proximal BFlh. The caudal-direction displacements of the BFlh in the dominant leg were reduced after the NHE training (from 3.98 ± 3.84 to 1.50 ± 4.17 mm, p < 0.05). The magnitude of reduction was associated with improved eccentric strength of the knee flexor muscle in the dominant leg (r = 0.63)., Conclusions: UST is a validated tool for measuring muscle displacement. NHE training decreased caudal-direction muscle displacement in the BFlh and increased eccentric strength., Competing Interests: Conflict of interest The BenQ ultrasound equipment used in this study is a donation from the BenQ Corp. to the College of Medicine, National Taiwan University (July 12, 2018). The corresponding author is a custodian and user of the equipment. There are no potential conflicts of interest among other authors., (Copyright © 2025. Published by Elsevier Inc.)

Objective: Near-field (NF) clutter filters are critical for unveiling true myocardial structure and dynamics. Randomized singular value decomposition (rSVD) stands out for its proven computational efficiency and robustness. This study investigates the effect of rSVD-based NF clutter filtering on myocardial motion estimation., Methods: In silico, material points and their displacements in a homogeneous medium under uniaxial compressions (0.5% - 9% axial strains at 0.5% increments) were simulated in finite-element models. They were exported to the k-Wave toolbox for simulations of pre- and post-deformed ultrasound images with/ without a realistic phase aberrating layer in a high-contrast diverging wave compounding scheme. In vivo, echocardiograms of 20 normal human hearts were acquired using a coded diverging wave compounding imaging method at 3200 frames/second in the transthoracic apical four-chamber view. Morphological component analysis (MCA), which is also a sparse representation method but computationally intensive, was used for comparison with rSVD. Both rSVD- and MCA-based filters were applied to beamformed ultrasound radio-frequency (RF) data before cross-correlation-based speckle tracking. Contrast-to-noise ratios (CNRs) and root-mean-square deviations (RMSDs) were computed from regions of interest to evaluate NF clutter filtering performance of rSVD and MCA., Results: In silico, 2-D displacements estimated from rSVD-based clutter-reduced image data showed strong agreement with ground truth (R 2 of 0.95). In vivo, CNR improvements ranged from 1.02 dB to 17.68 dB, consistently enhancing image quality across all subjects. An improvement of ∼4.9 dB in the apical segments was observed in 80% of cases. Mean RMSDs were below 5.0% for all rSVD-based NF clutter-reduced data. While both rSVD and MCA effectively filtered NF clutter, rSVD was significantly more practical., Conclusion: Our findings confirm the reliability, accuracy, and efficiency of rSVD-based clutter filtering in speckle tracking echocardiography. This underscores the feasibility of matrix decomposition-based methods, exemplified by rSVD, in NF clutter filtering for myocardial motion estimation., Competing Interests: Conflict of interest The authors declare no competing interests., (Copyright © 2024 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, chronic blood disorder. Symptoms such as fatigue can have a substantial impact on patients' physical activity levels, sleep, quality of life, and work productivity. Ravulizumab treatment can reduce thrombosis risk, improve survival and quality of life, and reduce fatigue in PNH, but information is limited on how it impacts sleep and physical activity. Here, data on resting heart rate, daily physical activity, and sleep in ravulizumab-treated patients with PNH were passively collected via a digital wearable activity-tracking device and patient-reported outcome (PRO) data were collected via weekly surveys in the same cohort., Methods: REVEAL was a 32-week prospective observational cohort study in individuals with PNH receiving ravulizumab in the USA. A wrist-worn Fitbit™ collected data on resting heart rate, daily step count, and sleep duration from eligible patients. Patients also completed the following electronic weekly surveys: Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue, Patient-Reported Outcomes Measurement Information System (PROMIS) Global Physical Health, PROMIS Global Mental Health, PROMIS Sleep-Related Impairment and Sleep Disturbance, and Work Productivity and Activity Impairment Questionnaire - Specific Health Problem (WPAI-SHP). Data collected from the activity trackers and surveys were compared against US general population values reported in the literature., Results: Twenty-eight ravulizumab-treated patients were included (median age: 34 years; 54% female). PRO scores were within US general population normative values, including FACIT-Fatigue (40.0), PROMIS Global Physical Health (51.0), Global Mental Health (51.0), Sleep-Related Impairment (50.0), and Sleep Disturbance (49.0). Similarly, mean resting heart rate (67 bpm), daily step count (7476), and sleep duration (7.7 h) were within the range of US general population values. Daily step count was positively correlated with PROMIS Global Physical and Mental Health scores., Conclusions: This was the first study to use digital monitoring technology to collect data on physical activity and sleep in patients with PNH. The findings indicate that ravulizumab treatment enables patients with PNH to achieve activity levels (heart rate, sleep duration, step count) and quality of life that are comparable to those of the US general population. A weak positive correlation was identified between patient-reported physical and mental health and daily physical activity levels., (© 2024. The Author(s).)

Background: Interprofessional education (IPE) has the potential to shape students' collaboration perception and interprofessional identity but remains understudied. This study aims to understand the effects of the IPE program as a contextual trigger to promote collaboration perception change and interprofessional identity formation among healthcare professional students., Methods: Using concurrent triangulation mixed-methods, we examined the relationship between collaboration perception and interprofessional identity change among health profession students (N = 263), and explored their perspectives on how their IPE experiences influenced their perception and identity. Participants completed the Interdisciplinary Education Perception Scale and Extended Professional Identity Scale and responded to open-ended questions before and after the IPE intervention. Pearson's correlation, t-tests, regression (quantitative), and thematic analysis (qualitative) were conducted., Results: Teams with initially lower collaboration perception (M = 3.59) and lower interprofessional identity (M = 3.59) showed a significant increase in collaboration perception (M = 3.76, t = 2.63; p = .02) and interprofessional identity (M = 3.97, t = 4.86; p < .001) after participating in IPE. The positive relationship between collaboration perception and interprofessional identity strengthened after participating in IPE, as evident from the correlation (Time 1: r = .69; p < .001; Time 2: r = .79; p < .001). Furthermore, collaboration perception in Time 1 significantly predicted the variance in interprofessional identity at Time 2 (β = 0.347, p < .001). Qualitative findings indicated that 85.2% of students expressed that IPE played a role in promoting their interprofessional identity and collaboration attitudes., Conclusions: Incorporating the IPE program into the curriculum can effectively enhance students' collaboration perception and interprofessional identity, ultimately preparing them for collaborative practice in the healthcare system. By engaging students in interprofessional teamwork, communication, and joint decision-making processes, the IPE program provides a valuable context for students to develop a sense of belonging and commitment to interprofessional collaboration., (© 2024. The Author(s).)

The widely used Vermon 1024-element matrix array for 3-D ultrasound imaging has three blank rows in the elevational direction, which breaks the elevation periodicity, thus degrading volumetric image quality. To bypass the blank rows in elevation while maintaining the steering capability in azimuth, we proposed a row-transmission (RT) scheme to improve 3-D spatial resolution. Specifically, we divided the full array into four apertures, each with multiple rows along the elevation. Each multirow aperture (MRA) was further divided into subapertures to transmit diverging waves (DWs) sequentially. Coherent DW compounding (CDWC) was realized in azimuth, while the elevation was multielement synthetic aperture (M-SA) imaging by regarding each row as an array of dashed line elements. An in-house spatiotemporal coding strategy, cascaded synthetic aperture (CaSA), was incorporated into the RT scheme as RT-CaSA to increase the signal-to-noise ratio (SNR). We compared the proposed RT with conventional bank-by-bank transmission-reception (Bank) and sparse-random-aperture compounding (SRAC) in a wire phantom and the in vivo human abdominal aorta (AA) to assess the performance of anatomical imaging and aortic wall motion estimation. Phantom results demonstrated superior lateral resolution achieved by our RT scheme (+19.52% and +16.88% versus Bank, +15.32% and +19.72% versus SRAC, in the azimuth-depth and elevation-depth planes, respectively). Our RT-CaSA showed excellent contrast ratios (CRs) (+8.19 and +8.08 dB versus Bank, +6.81 and +5.85 dB versus SRAC, +0.99 and +0.90 dB versus RT) and the highest in vivo aortic wall motion estimation accuracy. The RT scheme was demonstrated to have potential for various matrix array-based 3-D imaging research.

The coexistence of free chlorine and bromide under sunlight irradiation (sunlight/FC with Br - ) is unavoidable in outdoor seawater swimming pools, and the formation of brominated disinfection byproducts could act more harmful than chlorinated disinfection byproducts. In this study, benzotriazole was selected as a model compound to investigate the degradation rate and the subsequent formation of disinfection byproducts via sunlight/FC with Br - process. The rate constants for the degradation of benzotriazole under pseudo first order conditions in sunlight/FC with Br - and sunlight/FC are 2.3 ± 0.07 × 10 -1  min -1 and 6.0 ± 0.7 × 10 -2  min -1 , respectively. The enhanced degradation of benzotriazole can be ascribed to the generation of HO•, bromine species, and reactive halogen species (RHS) during sunlight/FC with Br - . Despite the fact that sunlight/FC with Br - process enhanced benzotriazole degradation, the reaction results in increasing tribromomethane (TBM) formation. A high concentration (37.8 μg/L) of TBM was detected in the sunlight/FC with Br - , which was due to the reaction of RHS. The degradation of benzotriazole was notably influenced by the pH value (pH 4 - 11), the concentration of bromide (0 - 2 mM), and free chlorine (1 - 6 mg/L). Furthermore, the concentration of TBM increased when the free chlorine concentrations increased, implying the formation potential of harmful TBM in chlorinated seawater swimming pools., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: Restricted tendon gliding is commonly observed in patients after finger flexor tendon (FFT) repair. The study described here was aimed at quantifying the amount of FFT gliding to evaluate the recovery of post-operative tendons using a 2-D radiofrequency (RF)-based ultrasound speckle tracking algorithm (UST)., Methods: Ex vivo uniaxial tensile testing of porcine flexor tendons and in vivo isometric testing of human FFT were implemented to verify the efficacy of UST beforehand. The verified UST was then applied to the patients after FFT repair to compare tendon gliding between affected and healthy sides and to investigate its correlation with the joint range of motion (ROM)., Results: Excellent validity was confirmed with the average R 2 value of 0.98, mean absolute error of 0.15 ± 0.08 mm and mean absolute percentage error of 5.19 ± 2.43% between results from UST and ex vivo testing. The test-retest reliability was verified with good agreement of ICC (0.90). The affected side exhibited less gliding (p = 0.001) and smaller active ROM (p = 0.002) than the healthy side. Meanwhile, a significant correlation between tendon gliding and passive ROM was found only on the healthy side (ρ = 0.711, p = 0.009)., Conclusion: The present study provides a promising protocol to evaluate post-operative tendon recovery by quantifying the amount of FFT gliding with a validated UST. FFT gliding in patients with different levels of ROM restriction should be further explored for categorizing the severity of tendon adhesion., Competing Interests: Conflict of interest The BenQ ultrasound equipment used in this study is a donation from the BenQ Corporation to the College of Medicine, National Taiwan University (July 12, 2018). H.K.W. is a custodian and user of the equipment. There are no potential conflicts of interest among the other authors., (Copyright © 2023 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Background: Collaboration between people with type 2 diabetes (T2DM) and their health care teams is important for optimal control of the disease and outcomes. Digital technologies could potentially tie together several health care-related devices and platforms into connected ecosystems (CES), but attitudes about CES are unknown., Objective: We surveyed convenience samples of patients and physicians to better understand which patient characteristics are associated with higher likelihoods of (1) participating in a potential CES program, as self-reported by patients with T2DM and (2) clinical benefit from participation in a potential CES program, as reported by physicians., Methods: Adults self-reporting a diagnosis of T2DM and current insulin use (n=197), and 33 physicians whose practices included ≥20% of such patients, were enrolled in the United States, France, and Germany. We surveyed both groups about the likelihood of patient participation in a CES. We then examined the associations between patients' clinical and sociodemographic characteristics and this likelihood. We also described characteristics of patients likely to clinically benefit from CES use, according to physicians., Results: Compared with patients in Germany and France, US patients were younger (mean age 45.3 [SD 11.9] years vs 61.9 [SD 9.2] and 65.8 [SD 9.4] years, respectively), more often female, more highly educated, and more often working full-time. In all, 51 (44.7%) US patients, 16 (36.4%) German patients, and 18 (46.3%) French patients indicated strong interest in a CES program, and 115 (78.7%) reported currently using ≥1 connected device or app. However, physicians believed that only 11.3%-19.2% of their patients were using connected devices or apps to manage their disease. Physicians also reported infrequently recommending or prescribing connected devices to their patients, although ≥80% (n=28) of them thought that a CES could help support their patients in managing their disease. The factors most predictive of patient likelihood of participating in a CES program were cost, inclusion of medication reminders, and linking blood glucose levels to behaviors such as eating and exercise. In all countries, the most common patient expectations for a CES program were that it could help them eat more healthfully, increase their physical activity, increase their understanding of how blood glucose relates to behavior such as exercise and eating, and reduce stress. Physicians thought that newly diagnosed patients, sicker patients-those who had been hospitalized for diabetes, were currently using insulin, or who had any comorbid condition-and patients who were nonadherent to treatment were most likely to benefit from CES use., Conclusions: In this study, there was a high degree of interest in the future use of CES, although additional education is needed among both patients with T2DM and their physicians to achieve the full potential of such systems to improve self-management and clinical care for the disease., (©Elizabeth Benito-Garcia, Julio Vega, Eric J Daza, Wei-Nchih Lee, Adee Kennedy, Jean-Marc Chantelot. Originally published in JMIR Formative Research (https://formative.jmir.org), 30.11.2023.)

Objective. A phased or a curvilinear array produces ultrasound (US) images with a sector field of view, which inherently exhibits spatially-varying image resolution with inferior quality in the far zone and towards the two sides azimuthally. Sector US images with improved spatial resolutions are favorable for accurate quantitative analysis of large and dynamic organs, such as the heart. Therefore, this study aims to translate US images with spatially-varying resolution to ones with less spatially-varying resolution. CycleGAN has been a prominent choice for unpaired medical image translation; however, it neither guarantees structural consistency nor preserves backscattering patterns between input and generated images for unpaired US images. Approach. To circumvent this limitation, we propose a constrained CycleGAN (CCycleGAN), which directly performs US image generation with unpaired images acquired by different ultrasound array probes. In addition to conventional adversarial and cycle-consistency losses of CycleGAN, CCycleGAN introduces an identical loss and a correlation coefficient loss based on intrinsic US backscattered signal properties to constrain structural consistency and backscattering patterns, respectively. Instead of post-processed B-mode images, CCycleGAN uses envelope data directly obtained from beamformed radio-frequency signals without any other nonlinear postprocessing. Main results . In vitro phantom results demonstrate that CCycleGAN successfully generates images with improved spatial resolution as well as higher peak signal-to-noise ratio and structural similarity compared with benchmarks. Significance . CCycleGAN-generated US images of the in vivo human beating heart further facilitate higher quality heart wall motion estimation than benchmarks-generated ones, particularly in deep regions. The codes are available athttps://github.com/xfsun99/CCycleGAN-TF2., (Creative Commons Attribution license.)

Direct and nondestructive assessment of material properties of skeletal muscle in vivo shall advance our understanding of intact muscle mechanics and facilitate personalized interventions. However, this is challenged by intricate hierarchical microstructure of the skeletal muscle. We have previously regarded the skeletal muscle as a composite of myofibers and extracellular matrix (ECM), formulated shear wave propagation in the undeformed muscle using the acoustoelastic theory, and preliminarily demonstrated that ultrasound-based shear wave elastography (SWE) could estimate microstructure-related material parameters (MRMPs): myofiber stiffness μ f , ECM stiffness μ m , and myofiber volume ratio V f . The proposed method warrants further validation but is hampered by the lack of ground truth values of MRMPs. In this study, we presented analytical and experimental validations of the proposed method using finite-element (FE) simulations and 3D-printed hydrogel phantoms, respectively. Three combinations of different physiologically relevant MRMPs were used in the FE simulations where shear wave propagations in the corresponding composite media were simulated. Two 3D-printed hydrogel phantoms with the MRMPs close to those of a real skeletal muscle (i.e., μ f =2.02kPa, μ m =52.42kPa, and V f =0.675,0.832) for ultrasound imaging were fabricated by an alginate-based hydrogel printing protocol that we modified and optimized from the freeform reversible embedding of suspended hydrogels (FRESH) method in literature. Average percent errors of (μ f ,μ m ,V f ) estimates were found to be (2.7%,7.3%,2.4%)in silico and (3.0%,8.0%,9.9%)in vitro. This quantitative study corroborated the potential of our proposed theoretical model along with ultrasound SWE for uncovering microstructural characteristics of the skeletal muscle in an entirely nondestructive way., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Singular value decomposition (SVD)-based filters have become the norm for clutter filtering in ultrasound blood flow applications but are computationally expensive and susceptible to large and fast tissue motion. Randomized SVD (rSVD) has later been shown to successfully accelerate filtering of in vivo stationary tissues. However, little is known about its performance on ultrafast echocardiography, which produces thousands of frames to assess complex myocardial deformation and blood dynamics. Neither has its inherently robust randomized scheme been proven in any ultrasound blood flow imaging methods. This study thus proposed to employ rSVD as a fast and robust clutter filter for ultrafast echocardiograms prior to power Doppler analysis. Ultrafast echocardiograms of nine normal human hearts were acquired in vivo by our cascaded synthetic aperture imaging method. One subject was additionally scanned under four different sonographic signal-to-noise ratio (SNR) levels. Contrast ratio (CR) and contrast-to-noise ratio (CNR) of in vivo power Doppler images obtained from filtered ultrafast echocardiograms were calculated, and their mean and standard deviation within a cardiac cycle represented temporal average and variation of contrast resolution, respectively. Our in vivo results showed that rSVD accelerated clutter filtering by 12-fold and provided significantly better local contrast (mean CNR values: p < 0.001) while being equally effective (mean CR values: p = 0.20) compared with full-SVD. rSVD yielded smaller standard deviations of CR (1.32 dB vs. 5.49 dB) and CNR (1.27 dB vs. 5.49 dB) than full-SVD in the lowest SNR scenario, thus substantiating its superior robustness. Our findings suggest using rSVD in ultrafast echocardiographic blood dynamics analysis., Competing Interests: Conflict of interest disclosure The authors declare no competing interests., (Copyright © 2022 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Accessibility of diagnostic screening and treatment monitoring devices for respiratory diseases is critical in promoting healthcare and reducing sudden complications and mortality. Spirometry is the standard for diagnosing and monitoring several lung diseases. However, it lacks regional assessment capabilities necessary for detecting subtle regional changes in certain diseases. It also requires challenging breathing maneuvers difficult for elderlies, children, and diseased patients. Here, we actualized an affordable, portable, and self-administrable electrical impedance tomography (EIT) system for home-based lung function assessment and telemedicine. Through simultaneous EIT-spirometry trials on healthy subjects, we demonstrated that our device can predict spirometry indicators over a wide range and can provide regional mapping of these indicators. We further developed a close-to-effortless breathing paradigm and tested it by longitudinally monitoring a COVID-19 discharged subject and two healthy controls with results suggesting the paradigm can detect initial deterioration followed by recovery. Overall, the EIT system can be widely applicable for lung function screening and monitoring both at homes and clinics., (© 2022. The Author(s).)

Background: Seasonal influenza affects 5% to 15% of Americans annually, resulting in preventable deaths and substantial economic impact. Influenza infection is particularly dangerous for people with cardiovascular disease, who therefore represent a priority group for vaccination campaigns., Objective: We aimed to assess the effects of digital intervention messaging on self-reported rates of seasonal influenza vaccination., Methods: This was a randomized, controlled, single-blind, and decentralized trial conducted at individual locations throughout the United States over the 2020-2021 influenza season. Adults with self-reported cardiovascular disease who were members of the Achievement mobile platform were randomized to receive or not receive a series of 6 patient-centered digital intervention messages promoting influenza vaccination. The primary end point was the between-group difference in self-reported vaccination rates at 6 months after randomization. Secondary outcomes included the levels of engagement with the messages and the relationship between vaccination rates and engagement with the messages. Subgroup analyses examined variation in intervention effects by race. Controlling for randomization group, we examined the impact of other predictors of vaccination status, including cardiovascular condition type, vaccine drivers or barriers, and vaccine knowledge., Results: Of the 49,138 randomized participants, responses on the primary end point were available for 11,237 (22.87%; 5575 in the intervention group and 5662 in the control group) participants. The vaccination rate was significantly higher in the intervention group (3418/5575, 61.31%) than the control group (3355/5662, 59.25%; relative risk 1.03, 95% CI 1.004-1.066; P=.03). Participants who were older, more educated, and White or Asian were more likely to report being vaccinated. The intervention was effective among White participants (P=.004) but not among people of color (P=.42). The vaccination rate was 13 percentage points higher among participants who completed all 6 intervention messages versus none, and at least 2 completed messages appeared to be needed for effectiveness. Participants who reported a diagnosis of COVID-19 were more likely to be vaccinated for influenza regardless of treatment assignment., Conclusions: This personalized, evidence-based digital intervention was effective in increasing vaccination rates in this population of high-risk people with cardiovascular disease., Trial Registration: ClinicalTrials.gov NCT04584645; https://clinicaltrials.gov/ct2/show/NCT04584645., (©Nell J Marshall, Jennifer L Lee, Jessica Schroeder, Wei-Nchih Lee, Jermyn See, Mohammad Madjid, Mrudula R Munagala, John D Piette, Litjen Tan, Orly Vardeny, Michael Greenberg, Jan Liska, Monica Mercer, Sandrine Samson. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 07.10.2022.)

Electrical impedance tomography (EIT) is a bio-medical imaging modality that has several clinical applications namely for human lungs. Yet, its relationship with gold standard lung diagnostic tools including spirometry is not available. In this study, simultaneous EIT and spirometry measurements were collected for 14 healthy subjects who performed forced breathing paradigms of different efforts simulating a wide range of spirometry indicators. It is demonstrated that EIT can predict standard spirometry indicators over a wide dynamic range, with a potential sensitivity and specificity of 98% and 100%, respectively, in detecting obstructive patterns. It is also shown that EIT can provide a regional mapping of the spirometry indicator which are shown to be consistent with their corresponding global indicators. Overall, EIT can predict spirometry indicators and can assess regional lung health through parametric mapping. Clinical Relevance- This study shows that EIT can infer standard spirometry indicators and potentially assess regional lung health. Therefore, EIT can be used for screening, diagnosis, and monitoring of obstructive and resistive lung diseases.

Objective: This study develops a biomedical ultrasound imaging method to infer microstructural information (i.e., tissue level) from imaging mechanical behavior of skeletal muscle (i.e., organ level)., Methods: We first reviewed the constitutive model of skeletal muscle by regarding it as a transversely isotropic (TI) hyperelastic composite material, for which a theoretical formula was established among shear wave speed, deformation, and material parameters (MPs) using the acoustoelasticity theory. The formula was evaluated by finite element (FE) simulations and experimentally examined using ultrasound shear wave imaging (SWI) and strain imaging (SI) on in vivo passive biceps brachii muscles of two healthy volunteers. The imaging sequence included 1) generation of SW in multiple propagation directions while resting the muscle at an elbow angle of 90°; 2) generation of SW propagating along the myofiber direction during continuous uniaxial muscle extension by passively changing the elbow angle from 90° to 120°. Ultrasound-quantified SW speeds and muscle deformations were fitted by the theoretical formula to estimate MPs of in vivo passive muscle., Results: Estimated myofiber stiffness, stiffness ratio of myofiber to extracellular matrix (ECM), and ECM volume ratio all agreed with literature findings., Conclusion: The proposed mathematical formula together with our in-house ultrasound imaging method enabled assessment of microstructural material properties of in vivo passive skeletal muscle from organ-level mechanical behavior in an entirely noninvasive way., Significance: Noninvasive assessment of both micro and macro properties of in vivo skeletal muscle will advance our understanding of complex muscle dynamics and facilitate treatment and rehabilitation planning.

Background: This study aimed to measure and compare (1) the microcirculation and microcirculatory responses of the muscles and tendons at rest and during isometric muscle contractions in participants with and without diabetes mellitus (DM) and (2) to determine correlations between microcirculation and muscle strength. Methods: Sixty-three participants with type 2 DM and 42 physically matched controls were recruited. Baseline measurements of the microcirculation of the rectus femoris (RF) and medial gastrocnemius (MG) muscles and patellar (PT) and Achilles tendons (AT), as well as their microcirculatory changes during maximal isometric exercises, were performed and recorded by using near-infrared spectroscopy and a red laser. Data on various laboratory tests (including glycated hemoglobin, triglyceride, high-density cholesterol), the monofilament test, and the ankle-brachial index were also obtained. Results: The baseline measurements indicated that, compared with the controls, the diabetic participants had lower oxygen saturation (SpO 2 ) in their RF and MG muscles (both P  < 0.001), and the total hemoglobin in the diabetic PT and AT was higher ( P  = 0.001 and P  = 0.01). The minimal SpO 2 levels in the aforementioned muscles during isometric contractions were lower in the diabetes group than in the control group ( P  ≤ 0.001). Furthermore, there were correlations between the microcirculatory change of the RF muscle and the knee extension force. Conclusions: This study demonstrated the effects of diabetes on the microcirculation of skeletal muscles and tendons during baseline measurements and responses to maximal isometric exercises. The results support the need for preventive strategies for diabetic muscles to prevent adverse complications when performing resistance training.

Another type of natural wave, traced from longitudinal wall motion and propagation along the artery, is observed in our in vivo human carotid artery experiments. We coin it as extension wave (EW) and hypothesize that EW velocity (EWV) is associated with arterial longitudinal stiffness. The EW is thus assumed to complement the pulse wave (PW), whose velocity (PWV) is tracked from the radial wall displacement and linked to arterial circumferential stiffness through the Moens-Korteweg equation, as indicators for arterial mechanical anisotropy quantification by noninvasive high-frame-rate ultrasound. The relationship between directional arterial stiffnesses and the two natural wave speeds was investigated in wave theory, finite-element simulations based on isotropic and anisotropic arterial models, and in vivo human common carotid artery ( n = 10) experiments. Excellent agreement between the theory and simulations showed that EWV was 2.57 and 1.03 times higher than PWV in an isotropic and an anisotropic carotid artery model, respectively, whereas in vivo EWV was consistently lower than PWV in all 10 healthy human subjects. A strong linear correlation was substantiated in vivo between EWV and arterial longitudinal stiffness quantified by a well-validated vascular-guided wave imaging technique (VGWI). We thereby proposed a novel index calculated as EWV 2 /PWV 2 as an alternative to assess arterial mechanical anisotropy. Simulations and in vivo results corroborated the effect of mechanical anisotropy on the propagation of spontaneous waves along the arterial wall. The proposed anisotropy index demonstrated the feasibility of the concurrent EW and PW imaged by high frame-rate ultrasound in grading of arterial wall anisotropy. NEW & NOTEWORTHY An extension wave formed by longitudinal wall displacements was observed by high-frame-rate ultrasound in the human common carotid artery in vivo. A strong correlation between extension wave velocity and arterial longitudinal stiffness complements the well-established pulse wave, which is linked to circumferential stiffness, to noninvasively assess direction-dependent wall elasticity of the major artery. The proposed anisotropy index, which directly reflects arterial wall microstructure and function, might be a potential risk factor for screening (sub-) clinical cardiovascular diseases.

Objective: Arterial wall deformation, stiffness, and luminal pressure are well-recognized predictors of cardiovascular diseases but intertwined. Establishing a relationship among these three predictors is therefore important for comprehensive assessment of the circulatory system, but very few studies focused on this., Methods: In this study, we first derived a mathematical description for localized luminal pressure change ( ∆p) as a function of arterial wall strains ( ε) and shear modulus ( μ T ) in the transverse plane; the arterial wall was modelled as a transversely isotropic and piecewise linearly-elastic material. Finite element simulations (FES) and in vitro fluid-driven inflation experiments were performed on arteries with both normal and abnormal geometries. ε and μ T in the experimental study were estimated by an ultrasound elastographic imaging framework (UEIF)., Results: FES results showed good accuracy (percent errors ≤ 6.42%) of the proposed method for all simulated artery models. Experimental results showed good repeatability and reproducibility. Estimated ∆p pp values (average peak-to-peak pressure change) compared with pressure meter measurements in two normal geometry phantoms and an excised aorta were 65.95 ± 4.29 mmHg vs. 66.45 ± 3.80 mmHg, 60.49 ± 1.82 mmHg vs. 59.92 ± 2.69, and 36.03 ± 1.90 mmHg vs. 38.8 ± 3.21 mmHg, respectively. For the artery with abnormal geometry mimicking a simple plaque shape, the feasibility of the proposed method for ∆p estimation was also validated., Conclusion: Results demonstrated that UEIF with the proposed mathematical model, which lumped wall deformation, stiffness and luminal pressure, could estimate the localized dynamic luminal pressure change noninvasively and accurately.

Understanding day-to-day variations in symptoms and medication management can be important in describing patient centered outcomes for people with constipation. Patient Generated Health Data (PGHD) from digital devices is a potential solution, but its utility as a tool for describing experiences of people with frequent constipation is unknown. We conducted a virtual, 16-week prospective study of individuals with frequent constipation from an online wellness platform that connects mobile consumer digital devices including wearable monitors capable of passively collecting steps, sleep, and heart rate data. Participants wore a Fitbit monitoring device for the study duration and were administered daily and monthly surveys assessing constipation symptom severity and medication usage. A set of 38 predetermined day-level behavioral activity metrics were computed from minute-level data streams for steps, sleep and heart rate. Mixed effects regression models were used to compare activity metrics between constipation status (irregular or constipated vs. regular day), medication use (medication day vs. non-medication day) and the interaction of medication day with irregular or constipation days, as well as to model likelihood to treat with constipation medications based on daily self-reported symptom severity. Correction for multiple comparisons was performed with the Benjamini-Hochberg procedure for false discovery rate. This study analyzed 1540 enrolled participants with completed daily surveys (mean age 36.6 sd 10.0, 72.8% female, 88.8% Caucasian). Of those, 1293 completed all monthly surveys and 756 had sufficient Fitbit data density for analysis of activity metrics. At a daily-level, 22 of the 38 activity metrics were significantly associated with bowel movement or medication treatment patterns for constipation. Participants were measured to have fewer steps on irregular days compared to regular days (-200 steps, 95% CI [-280, -120]), longer periods of inactivity on constipated days (9.1 min, 95% CI [5.2, 12.9]), reduced total sleep time on irregular and constipated days (-2.4 min, 95% CI [-4.3, -0.4] and -4.0 min, 95% CI [-6.5, -1.4], respectively). Participants reported greater severity of symptoms for bloating, hard stool, difficulty passing, and painful bowel movements on irregular, constipation and medication days compared to regular days with no medication. Interaction analysis of medication days with irregular or constipation days observed small increases in severity compared to non-medication days. Participants were 4.3% (95% CI 3.2, 5.3) more likely to treat with medication on constipated days versus regular. No significant increase in likelihood was observed for irregular days. Daily likelihood to treat increased for each 1-point change in symptom severity of bloating (2.4%, 95% CI [2.0, 2.7]), inability to pass (2.2%, 95% CI [1.4, 3.0]) and incomplete bowel movements (1.3%, 95% CI [0.9, 1.7]). This is the first large scale virtual prospective study describing the association between passively collected PGHD and constipation symptoms and severity at a day-to-day granularity level. Constipation status, irregular or constipated, was associated with a number of activity metrics in steps and sleep, and likelihood to treat with medication increased with increasing severity for a number of constipation symptoms. Given the small magnitude of effect, further research is needed to understand the clinical relevance of these results. PGHD may be useful as a tool for describing real world patient centered experiences for people with constipation.

Background: We describe the impact of influenza on medical outcomes and daily activities among people with and without type 2 diabetes mellitus (T2DM)., Methods: Retrospective cohort analysis of a US health plan offering a digital wellness platform connecting wearable devices capable of tracking steps, sleep, and heart rate. For the 2016 to 2017 influenza season, we compared adults with T2DM to age and gender matched controls. Medical claims were used to define cohorts and identify influenza events and outcomes. Digital tracking data were aggregated at time slices of minute-, day-, week-, and year-level. A pre-post study design compared the peri-influenza period (two weeks before and four weeks after influenza diagnosis) to the six-week preceding period (baseline)., Results: A total of 54 656 T2DM and 113 016 non-DM controls were used for the study. People with T2DM had more influenza claims, vaccinations, and influenza antivirals per 100 people (1.96% vs 1.37%, 34.3% vs 24.3%, and 27.1 vs 22 respectively, P < .001). A total of 1086 persons with T2DM and 1567 controls had an influenza claim (47.4% male, median age 54, 6.4% vs 7.8% trackers, respectively). Glycemic events, pneumonia, and ischemic heart disease increased over baseline during the peri-influenza period for T2DM (1.74-, 7.4-, and 1.6-fold increase respectively, P < .01). In a device wearing subcohort, we observed 10 000 fewer steps surrounding the influenza event, with the lowest (5500 steps) two days postinfluenza. Average heart rate increased significantly (+5.5 beats per minute) one day prior to influenza., Conclusion: Influenza increases rates of pneumonia, heart disease, and abnormal glucose levels among people with T2DM, and negatively impacts daily activities compared to controls.

Background: Depression and anxiety greatly impact daily behaviors, such as sleep and activity levels. With the increasing use of activity tracking wearables among the general population, there has been a growing interest in how data collected from these devices can be used to further understand the severity and progression of mental health conditions., Objective: This virtual 1-year observational study was designed with the objective of creating a longitudinal data set combining self-reported health outcomes, health care utilization, and quality of life data with activity tracker and app-based behavioral data for individuals with depression and anxiety. We provide an overview of the study design, report on baseline health and behavioral characteristics of the study population, and provide initial insights into how behavioral characteristics differ between groups of individuals with varying levels of disease severity., Methods: Individuals who were existing members of an online health community (Achievement, Evidation Health Inc) and were 18 years or older who had self-reported a diagnosis of depression or anxiety were eligible to enroll in this virtual 1-year study. Participants agreed to connect wearable activity trackers that captured data related to physical activity and sleep behavior. Mental health outcomes such as the Patient Health Questionnaire (PHQ-9), the Generalized Anxiety Disorder Questionnaire (GAD-7), mental health hospitalizations, and medication use were captured with surveys completed at baseline and months 3, 6, 9, and 12. In this analysis, we report on baseline characteristics of the sample, including mental health disease severity and health care utilization. Additionally, we explore the relationship between passively collected behavioral data and baseline mental health status and health care utilization., Results: Of the 1304 participants enrolled in the study, 1277 individuals completed the baseline survey and 1068 individuals had sufficient activity tracker data. Mean age was 33 (SD 9) years, and the majority of the study population was female (77.2%, 994/1288) and identified as Caucasian (88.3%, 1137/1288). At baseline, 94.8% (1211/1277) of study participants reported experiencing depression or anxiety symptoms in the last year. This baseline analysis found that some passively tracked behavioral traits are associated with more severe forms of anxiety or depression. Individuals with depressive symptoms were less active than those with minimal depressive symptoms. Severe forms of depression were also significantly associated with inconsistent sleep patterns and more disordered sleep., Conclusions: These initial findings suggest that longitudinal behavioral and health outcomes data may be useful for developing digital measures of health for mental health symptom severity and progression., (©Shefali Kumar, Jennifer L A Tran, Ernesto Ramirez, Wei-Nchih Lee, Luca Foschini, Jessie L Juusola. Originally published in JMIR Mental Health (http://mental.jmir.org), 23.07.2020.)

Low back pain is one of most common musculoskeletal disorders around the world. One major problem clinicians face is the lack of objective assessment modalities. Computed tomography and magnetic resonance imaging are commonly utilized but are unable to clearly distinguish patients with low back pain from healthy patients with respect to abnormalities. The reason may be the anisotropic nature of muscles, which is altered in function, and the scans provide only structural assessment. In view of this, ultrasound may be helpful in understanding the disease as it is performed in real-time and comprises different modes that measure thickness, blood flow and stiffness. By the use of ultrasound, patients with low back pain have been found to differ from healthy patients with respect to the thickness and stiffness of the transversus abdominis, thoracolumbar fascia and multifidus. The study results are currently still not conclusive, and further study is necessary to validate. Future work should focus on quantitative assessment of these tissues to provide textural, structural, hemodynamic and mechanical studies of low back pain. This review highlights the current understanding of how medical ultrasound has been used for diagnosis and study of low back pain and discusses potential new applications., (Copyright © 2020 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

The geometry and stiffness of a vessel are pertinent to blood dynamics and vessel wall mechanical behavior and may alter in diseased conditions. Ultrasound-based ultrafast Doppler (uDoppler) imaging and shear wave imaging (SWI) techniques have been extensively exploited for the assessment of vascular hemodynamics and mechanics. Their performance is conventionally validated on vessel-mimicking phantoms (VMPs) prior to their clinical use. Compared with commercial ones, customized VMPs are favored for research use because of their wider range of material properties, more complex lumen geometries, or wall structures. Fused deposition modeling (FDM) 3D printing technique with plastic filaments is a promising method for making VMPs with a complex vessel lumen. However, it may require a toxic solvent or a long dissolution time currently. In this paper, we present a safe, efficient and geometrically flexible method where FDM 3D printing with a water-soluble polyvinyl alcohol (PVA) filament is exploited to fabricate a walled three-branch VMP (VMP-I). As a key step in fabrication, to avoid dissolution of the PVA-printed vessel core by the solution of the tissue-mimicking material, paraffin wax was used for isolation. Paraffin wax is easy to coat (i.e. without any special equipment), of satisfactory thickness (∼0.1 mm), chemically stable, and easy to remove after fabrication, thus making the proposed method practicable for ultrasound imaging studies. VMP-I was examined by B-mode imaging and power Doppler imaging (PDI) to verify complete dissolution of PVA-printed vessel core in its lumen, confirming good fabrication quality. The flow velocities in VMP-I were estimated by uDoppler imaging with a -0.8% difference, and the shear wave propagation speeds for the same phantom were estimated by SWI with a -6.03% difference when compared with fluid-structure interaction (FSI) simulation results. A wall-less VMP of a scaled and simplified coronary arterial network (VMP-II) was additionally fabricated and examined to test the capability of the proposed method for a complex lumen geometry. The proposed fabrication method for customized VMPs is foreseen to facilitate the development of ultrasound imaging techniques for blood vessels.

While health-care providers have used incentives in an attempt to motivate patients to obtain vaccinations, their effect on vaccination rates has not been systematically evaluated on a large scale. In this study, we examined whether mobile applications may improve population vaccination rates through enhanced communication and incentives education. Our study is the first randomized controlled trial assessing the effect of large-scale messaging combined with individualized incentives on influenza-vaccination rates. In this trial, we delivered messages regarding influenza vaccinations to 50,286 adults, aged 18 through 65, then compared the subsequent vaccination rate, the effectiveness of the message content and the timing. Multiple rounds of messaging occurred over a seven-week period during the 2016 flu season, after which vaccination rates were observed for one week. Participants were randomly assigned to one of three messaging approaches: conspicuous (highlighting the amount of rewards to be received for obtaining a flu shot); generic (promoting vaccinations with no mention of rewards); or no-message. Evidence of vaccination obtainment was indicated by medical and pharmacy claims, augmented by patients self-reporting through the mobile wellness app during the study period. Of the people assigned to receive messaging, 23.2% obtained influenza vaccination, compared to 22.0% of people who obtained vaccination in the no-messaging control arm. This difference was statistically significant (p < 0.01). The research revealed that messaging effectiveness decreased after each successive batch sent, suggesting that most participants responsive to messaging would become activated immediately after receiving one alert. Interestingly, in this large-scale study, there were no significant differences between conspicuous incentives and generic messaging, suggesting an important area for future research. Trial Registration: clinicaltrials.gov identifier: NCT02908893., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: None., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Public lavatories may cause the spread of infectious pathogens because they are enclosed spaces that both healthy people and patients can use. Thus, surface analysis for microbial contamination in public lavatories is of great importance because it is considered as an indicator of hygiene control. Herein, we developed polymerase chain reaction (PCR)-compatible surface sample preparation tools to increase the detection sensitivity and reproducibility within a short time using a semi-automatic detection system. The bacteria and viruses on different surfaces were collected using half A4-sized wipes. The wipes were treated through four different processes in a cartridge: (1) the pathogens were transferred from the wipes to the aqua phase using simple gentle vortexing; (2) the bacteria and viruses were concentrated by adsorption on the graphene surface; (3) the pathogens on the graphene layer were perfectly lysed using bead-beating tools and (4) the released DNA/RNA was collected in a microtube. The prepared nucleic acid sample was amplified using PCR or loop-mediated isothermal amplification (LAMP). At least one order of magnitude higher sensitivity was achieved using the wipe collecting method compared to that achieved using the normal swab method. This was confirmed using a semi-automatic cartridge for the wipe sampling in a lavatory hygiene test.

The heart is an organ with highly dynamic complexity, including cyclic fast electrical activation, muscle kinematics, and blood dynamics. Although ultrafast cardiac imaging techniques based on pulsed-wave ultrasound (PUS) have rapidly emerged to permit mapping of heart dynamics, they suffer from limited sonographic signal-to-noise ratio (SNR) and penetration due to insufficient energy delivery and inevitable attenuation through the chest wall. We hereby propose ultrafast cascaded-wave ultrasound (uCUS) imaging to depict heart dynamics in higher SNR and larger penetration than conventional ultrafast PUS. To solve the known tradeoff between the length of transmitted ultrasound signals and spatial resolution while achieving ultrafast frame rates (>1000 Hz), we develop a cascaded synthetic aperture (CaSA) imaging method. In CaSA, an array probe is divided into subapertures; each subaperture transmits a train of diverging waves. These diverging waves are weighted in both the aperture (i.e., spatial) and range (i.e., temporal) directions with a coding matrix containing only +1 and -1 polarity coefficients. A corresponding spatiotemporal decoding matrix is designed to recover backscattered signals. The decoded signals are thereafter beamformed and coherently compounded to obtain one high-SNR beamformed image frame. For CaSA with M subapertures and N cascaded diverging waves, sonographic SNR is increased by 10× log 10 (N ×M) (dB) compared with conventional synthetic aperture (SA) imaging. The proposed uCUS with CaSA was evaluated with conventional SA and Hadamard-encoded SA (H-SA) methods in a calibration phantom for B-mode image quality and an in vivo human heart in a transthoracic setting for the quality assessment of anatomical, myocardial motion, and chamber blood power Doppler images. Our results demonstrated that the proposed uCUS with CaSA (4 subapertures, 32 cascaded waves) improved SNR (+20.46 dB versus SA, +14.83 dB versus H-SA) and contrast ratio (+8.44 dB versus SA, +7.81 dB versus H-SA) with comparable spatial resolutions to and at the same frame rates as benchmarks.

The formation of toxic disinfection by-products (DBPs) is among the main concerns in the use of chlorine sanitizers for washing fresh and fresh-cut produce to minimize microbial cross-contamination. Even so, robust analytical methods for measuring various DBPs in produce have been lacking. This study has established two liquid-liquid extraction methods, followed by gas chromatography with electron capture detection, to measure 32 conventional and emerging DBPs in different produce types including lettuce, cabbage and strawberry. Good recoveries (50-130%) were achieved for most DBPs in the different produce. The method detection limits were in the range of 0.3-10 ng/g for trihalomethanes, haloacetic acids, nitrogenous DBPs, and other carbonaceous DBPs. Preliminary screening analysis indicated one-third of the target DBPs were found in unwashed produce, and washing with chlorine significantly promoted DBPs' formation and concentrations in the produce. The developed analytical methods will be useful tools for future research on food DBPs., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Contamination of drinking water with pharmaceuticals and personal care products (PPCPs) is an issue of health concerns. To effectively control the level of PPCPs in drinking water, a pilot study employing two parallel trains of two-stage biofiltration, i.e., a sand/anthracite (SA) biofilter coupled with a biologically-active granular activated carbon (GAC) post-filter contactor, was conducted as a post-treatment after coagulation in a drinking water treatment plant. Results showed the biofiltration process could effectively remove PPCPs with an average removal of 53.4%, where the GAC contactor played the dominant role to remove 48.1% of the total PPCPs. The molecular properties determined the removability of individual PPCPs, i.e., smaller molecules with simpler structure connectivity were more likely to be removed. Based on the quantitative structure-property relationships (QSPRs) analysis, a simple regression model was proposed to predict the removability of each PPCP across the biofiltration process. The drinking water equivalent level (DWEL) quotient method was developed to assess the health risks of detected PPCPs in water samples. The biofiltration process showed efficient capacity to reduce the health risks of PPCPs with an average removal of 79%, and the PPCPs in the effluents generally would not pose adverse health effects. Pearson correlation analysis explored the possible role of nitrogenous PPCPs (N-PPCPs) as the precursors of nitrogenous disinfection byproducts (N-DBPs) in drinking waters. Aromatic nitrogen in PPCPs was found to be a significant descriptor for the formation potential of trichloroacetonitrile (TCAN). In addition, it was found that pre-filter chlorination could slightly improve the biofiltration of PPCPs., (Copyright © 2019. Published by Elsevier B.V.)

Studies of non-destructive bidirectional ultrasound assessment of non-linear mechanical behavior of the artery are scarce in the literature. We hereby propose derivation of a strain-shear modulus relationship as a new graphical diagnostic index using an ultrasound elastographic imaging framework, which encompasses our in-house bidirectional vascular guided wave imaging (VGWI) and ultrasound strain imaging (USI). This framework is used to assess arterial non-linearity in two orthogonal (i.e., longitudinal and circumferential) directions in the absence of non-invasive pressure measurement. Bidirectional VGWI estimates longitudinal (μ L ) and transverse (μ T ) shear moduli, whereas USI estimates radial strain (ɛ r ). Vessel-mimicking phantoms (with and without longitudinal pre-stretch) and in vitro porcine aortas under static and/or dynamic physiologic intraluminal pressure loads were examined. ɛ r was found to be a suitable alternative to intraluminal pressure for representation of cyclic loading on the artery wall. Results revealed that μ T values of all samples examined increased non-linearly with ε r magnitude and more drastically than μ L , whereas μ L values of only the pre-stretched phantoms and aortas increased with ɛ r magnitude. As a new graphical representation of arterial non-linearity and function, strain-shear modulus loops derived by the proposed framework over two consecutive dynamic loading cycles differentiated sample pre-conditions and corroborated direction-dependent non-linear mechanical behaviors of the aorta with high estimation repeatability., (Copyright © 2019 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Guided wave imaging for the artery remains in its infancy in clinical practice mainly because of complex arterial microstructure, hemodynamics and boundary conditions. Despite the theoretically known potential effect of the surrounding medium on guided wave propagation in thin media in non-destructive testing, experimental evidence pertaining to thin soft materials, such as the artery, is relatively scarce in the relevant literature. Therefore, this study first evaluated the propagating guided wave generated by acoustic radiation force in polyvinyl alcohol-based hydrogel plates differing in thickness and stiffness under various material coupling conditions (water and polyvinyl alcohol bulk). A thin-walled polyvinyl alcohol hollow cylindrical phantom coupled by softer gelatin-agar phantoms and an excised porcine aorta surrounded by water and pork belly were further examined. Guided waves in the thin structure and shear waves in the bulk media were captured by ultrafast ultrasound imaging, and guided wave dispersion as a function of the frequency-thickness product was analyzed using the zero-order anti-symmetric Lamb wave model to estimate the shear modulus of each thin medium studied. Results confirmed the deviated shear modulus estimates from the ground truth for thin plates, the thin-walled hollow cylindrical phantom and the porcine aorta bounded by stiffness-unmatched bulk medium. The findings indicated the need for (i) careful interpretation of estimated shear moduli of thin structure bounded by bulk media and (ii) a generalized guided wave model that takes into account the effect of coupling medium., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The United Kingdom National Review of Asthma Deaths (NRAD) recommends that patients who require ≥3 courses of oral corticosteroids (OCS) for exacerbations in the past year or those on British Thoracic Society (BTS) Step 4/5 treatment must be referred to a specialist asthma service. The aim of the study was to identify the proportion of asthma patients in primary care that fulfil NRAD criteria for specialist referral and factors associated with frequent exacerbations. A total of 2639 adult asthma patients from 10 primary care practices in Glasgow, UK were retrospectively studied between 2014 and 2015. Frequent exacerbators and short-acting β 2 -agonist (SABA) over-users were identified if they received ≥2 confirmed OCS courses for asthma and ≥13 SABA inhalers in the past year, respectively. Community dispensing data were used to assess treatment adherence defined as taking ≥75% of prescribed inhaled corticosteroid (ICS) dose. The study population included 185 (7%) frequent exacerbators, 137 (5%) SABA over-users, and 319 (12%) patients on BTS Step 4/5 treatment. Among frequent exacerbators, 41% required BTS Step 4/5 treatment, 46% had suboptimal ICS adherence, 42% had not attended an asthma review in the past year and 42% had no previous input from a specialist asthma service. Older age, female gender, BTS Step 4/5, SABA over-use and co-existing COPD diagnosis increased the risk of frequent exacerbations independently. Fourteen per 100 asthma patients would fulfil the NRAD criteria for specialist referral. Better collaboration between primary and secondary care asthma services is needed to improve chronic asthma care.

Natural organic matter (NOM) is known to cause major problems with drinking water quality management, such as sedimentation of disinfectants during the purification process, microbial growth of water pipes, and corrosion of pipes. For efficient and continuous removal of NOM from drinking water, a packed bed-type platform containing microbeads based on nanostructured zinc oxide (ZnO) was developed. ZnO was synthesized on graphene oxide (GO)-coated microbeads by optimizing the ZnO concentration and reaction time. The morphology of the synthesized ZnO-coated microbeads was confirmed by scanning electron microscopy, and an adsorption test was conducted using a cationic dye. The ZnO/GO microbeads were packed in a microtube. A humic acid contaminated aqueous solution was allowed to flow through the microbeads, and its removal rate was measured by UV-vis spectroscopy. This study confirmed that the purification platform containing ZnO removed more than 90% of humic acid of about 1,000 ppm.