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Complex motor commands for human locomotion are generated through the combination of motor modules representable as muscle synergies. Recent data have argued that muscle synergies are inborn or determined early in life, but development of the neuro-musculoskeletal system and acquisition of new skills may demand fine-tuning or reshaping of the early synergies. We seek to understand how locomotor synergies change during development and training by studying the synergies for running in preschoolers and diverse adults from sedentary subjects to elite marathoners, totaling 63 subjects assessed over 100 sessions. During development, synergies are fractionated into units with fewer muscles. As adults train to run, specific synergies coalesce to become merged synergies. Presences of specific synergy-merging patterns correlate with enhanced or reduced running efficiency. Fractionation and merging of muscle synergies may be a mechanism for modifying early motor modules (Nature) to accommodate the changing limb biomechanics and influences from sensorimotor training (Nurture). Motor commands for human locomotion are generated by combination of muscle synergies. In humans, muscle synergies for running exhibit considerable plasticity during child-to-adult development and adult training to meet the constantly changing biomechanical and efficiency demands.

What was once a science fiction fantasy, virtual reality (VR) technology has evolved and come a long way. Together with augmented reality (AR) technology, these simulations of an alternative environment have been incorporated into rehabilitation treatments. The introduction of head-mounted displays has made VR/AR devices more intuitive and compact, and no longer limited to upper-limb rehabilitation. However, there is still limited evidence supporting the use of VR and AR technology during locomotion, especially regarding the safety and efficacy relating to walking biomechanics. Therefore, the objective of this study is to explore the limitations of such technology through gait analysis. In this study, thirteen participants walked on a treadmill in normal, virtual and augmented versions of the laboratory environment. A series of spatiotemporal parameters and lower-limb joint angles were compared between conditions. The center of pressure (CoP) ellipse area (95% confidence ellipse) was significantly different between conditions (p = 0.002). Pairwise comparisons indicated a significantly greater CoP ellipse area for both the AR (p = 0.002) and VR (p = 0.005) conditions when compared to the normal laboratory condition. Furthermore, there was a significant difference in stride length (p<0.001) and cadence (p<0.001) between conditions. No statistically significant difference was found in the hip, knee and ankle joint kinematics between the three conditions (p>0.082), except for maximum ankle plantarflexion (p = 0.001). These differences in CoP ellipse area indicate that users of head-mounted VR/AR devices had difficulty maintaining a stable position on the treadmill. Also, differences in the gait parameters suggest that users walked with an unusual gait pattern which could potentially affect the effectiveness of gait rehabilitation treatments. Based on these results, position guidance in the form of feedback and the use of specialized treadmills should be considered when using head-mounted VR/AR devices.

A 9-valent human papillomavirus-6/11/16/18/31/33/45/52/58 (9vHPV) vaccine extends coverage to 5 next most common oncogenic types (31/33/45/52/58) in cervical cancer versus quadrivalent HPV (qHPV) vaccine. We describe efficacy, immunogenicity, and safety in Asian participants (India, Hong Kong, South Korea, Japan, Taiwan, and Thailand) from 2 international studies: a randomized, double-blinded, qHPV vaccine-controlled efficacy study (young women aged 16-26 years; NCT00543543; Study 001); and an immunogenicity study (girls and boys aged 9-15 years; NCT00943722; Study 002). Participants (N = 2519) were vaccinated at day 1 and months 2 and 6. Gynecological samples (Study 001 only) and serum were collected for HPV DNA and antibody assessments, respectively. Injection-site and systemic adverse events (AEs) were monitored. Data were analyzed by country and vaccination group. 9vHPV vaccine prevented HPV-31/33/45/52/58-related persistent infection with 90.4%-100% efficacy across included countries. At month 7, ≥97.9% of participants seroconverted for each HPV type. Injection-site AEs occurred in 77.7%-83.1% and 81.9%-87.5% of qHPV and 9vHPV vaccine recipients in Study 001, respectively, and 62.4%-85.7% of girls/boys in Study 002; most were mild to moderate. The 9vHPV vaccine is efficacious, immunogenic, and well tolerated in Asian participants. Data support 9vHPV vaccination programs in Asia. NCT00543543; NCT00943722.

Wireless accelerometers with various operating ranges have been used to measure tibial acceleration. Accelerometers with a low operating range output distorted signals and have been found to result in inaccurate measurements of peaks. A restoration algorithm using spline interpolation has been proposed to restore the distorted signal. This algorithm has been validated for axial peaks within the range of 15.0–15.9 g. However, the accuracy of peaks of higher magnitude and the resultant peaks have not been reported. The purpose of the present study is to evaluate the measurement agreement of the restored peaks using a low-range accelerometer (±16 g) against peaks sampled using a high-range accelerometer (±200 g). The measurement agreement of both the axial and resultant peaks were examined. In total, 24 runners were equipped with 2 tri-axial accelerometers at their tibia and completed an outdoor running assessment. The accelerometer with an operating range of ±200 g was used as reference. The results of this study showed an average difference of −1.40 ± 4.52 g and −1.23 ± 5.48 g for axial and resultant peaks. Based on our findings, the restoration algorithm could skew data and potentially lead to incorrect conclusions if used without caution.

Wearable sensors are an emerging technology, with growing evidence supporting their application in sport performance enhancement. This study utilized data collected from a tri-axial inertial sensor on the wrist of ten recreational and eight professional basketball players while they performed free-throws, to classify their skill levels. We employed a fully connected convolutional neural network (CNN) for the classification task, using 64% of the data for training, 16% for validation, and the remaining 20% for testing the model’s performance. In the case of considering a single parameter from the inertial sensor, the most accurate individual components were upward acceleration (AX), with an accuracy of 82% (sensitivity = 0.79; specificity = 0.84), forward acceleration (AZ), with an accuracy of 80% (sensitivity = 0.78; specificity = 0.83), and wrist angular velocity in the sagittal plane (GY), with an accuracy of 77% (sensitivity = 0.73; specificity = 0.79). The highest accuracy of the classification was achieved when these CNN inputs utilized a stack-up matrix of these three axes, resulting in an accuracy of 88% (sensitivity = 0.87, specificity = 0.90). Applying the CNN to data from a single wearable sensor successfully classified basketball players as recreational or professional with an accuracy of up to 88%. This study represents a step towards the development of a biofeedback device to improve free-throw shooting technique.

During human locomotor development, neonatal neuromotor control modules known as muscle synergies are continuously modified into their mature forms to enable independent walking. How the early muscle synergies, developing neuromusculoskeletal systems, and sensorimotor plasticity interact to regulate this process remains unknown. To address this, we investigated concurrent changes in muscle synergies, kinematic synergies, and lower-limb biomechanical properties across 4 stages of supported and independent walking through longitudinal bilateral multi-muscle recording, kinematic tracking, and personalized neuro-musculoskeletal modelling in 11 human infants, while incorporating additional data from adults and elders for a whole-lifespan analysis. Our results argue that the initially bilaterally asymmetrical muscle synergies and limb biomechanical properties co-evolve to ultimately result in symmetrical kinematic synergies that may stabilize gait. Functional symmetrization of neuromotor modules may be a reflection of the co-development of muscle synergies, their associated kinematic functions, and limb biomechanical properties for achieving gait stability and control efficiency throughout the lifespan. This study reveals that during human gait development, neuromotor modules (muscle synergies) and limb biomechanical properties co-evolve toward bilateral symmetry, which enhances locomotor stability. By combining longitudinal EMG, kinematic, and neuromusculoskeletal modeling data from infants, adults, and elders, the authors demonstrate that functional symmetrization of these modules underlies efficient and stable gait control across the lifespan.

The present study compared the effect between walking exercise and a newly developed sensor-based gait retraining on the peaks of knee adduction moment (KAM), knee adduction angular impulse (KAAI), knee flexion moment (KFM) and symptoms and functions in patients with early medial knee osteoarthritis (OA). Eligible participants (n = 71) with early medial knee OA (Kellgren-Lawrence grade I or II) were randomized to either walking exercise or gait retraining group. Knee loading-related parameters including KAM, KAAI and KFM were measured before and after 6-week gait retraining. We also examined clinical outcomes including visual analog pain scale (VASP) and Knee Injury and Osteoarthritis Outcome Score (KOOS) at each time point. After gait retraining, KAM1 and VASP were significantly reduced (both Ps < 0.001) and KOOS significantly improved (p = 0.004) in the gait retraining group, while these parameters remained similar in the walking exercise group (Ps ≥ 0.448). However, KAM2, KAAI and KFM did not change in both groups across time (Ps ≥ 0.120). A six-week sensor-based gait retraining, compared with walking exercise, was an effective intervention to lower medial knee loading, relieve knee pain and improve symptoms for patients with early medial knee OA.

This study introduced a novel but simple method to continuously measure footstrike patterns in runners using inexpensive force sensors. Two force sensing resistors were firmly affixed at the heel and second toe of both insoles to collect the time signal of foot contact. A total of 109 healthy young adults (42 males and 67 females) were recruited in this study. They ran on an instrumented treadmill at 0°, +10°, and -10° inclinations and attempted rearfoot, midfoot, and forefoot landings using real time visual biofeedback. Intra-step strike index and onset time difference between two force sensors were measured and analyzed with univariate linear regression. We analyzed 25,655 footfalls and found that onset time difference between two sensors explained 80-84% of variation in the prediction model of strike index (R-squared = 0.799-0.836, p<0.001). However, the time windows to detect footstrike patterns on different surface inclinations were not consistent. These findings may allow laboratory-based gait retraining to be implemented in natural running environments to aid in both injury prevention and performance enhancement.

Endometrial cancer is the third most common gynecologic malignancy and the ninth most common malignancy for females overall in Hong Kong. Approximately 80% or more of these cancers are endometrioid endometrial adenocarcinomas. The aim of this study was to reveal genes contributing to the development of endometrioid endometrial cancer, which may impact diagnosis, prognosis and treatment of the disease. Whole-genome gene expression analysis was completed for a set of 55 microdissected sporadic endometrioid endometrial adenocarcinomas and 29 microdissected normal endometrium specimens using the Affymetrix Human U133 Plus 2.0 oligonucleotide microarray. Selected genes of interest were validated by quantitative real-time-polymerase chain reaction (qRT-PCR). Pathway analysis was performed to reveal gene interactions involved in endometrial tumorigenesis. Unsupervised hierarchical clustering displayed a distinct separation between the endometrioid adenocarcinomas and normal endometrium samples. Supervised analysis identified 117 highly differentially regulated genes (⩾4.0-fold change), which distinguished the endometrial cancer specimens from normal endometrium. Twelve novel genes including DKK4, ZIC1, KIF1A, SAA2, LOC16378, ALPP2, CCL20, CXCL5, BST2, OLFM1, KLRC1 and MBC45780 were deregulated in the endometrial cancer, and further validated in an independent set of 56 cancer and 29 normal samples using qRT-PCR. In addition, 10 genes were differentially regulated in late-stage cancer, as compared to early-stage disease, and may be involved in tumor progression. Pathway analysis of the expression data from this tumor revealed an interconnected network consisting of 21 aberrantly regulated genes involved in angiogenesis, cell proliferation and chromosomal instability. The results of this study highlight the molecular features of endometrioid endometrial cancer and provide insight into the events underlying the development and progression of endometrioid endometrial cancer.

There is evidence that lesions of the nucleus accumbens core (AcbC) promote preference for smaller earlier reinforcers over larger delayed reinforcers in inter-temporal choice paradigms. It is not known whether this reflects an effect of the lesion on the rate of delay discounting, on sensitivity to reinforcer magnitude, or both. We examined the effect of AcbC lesions on inter-temporal choice using a quantitative method that allows effects on delay discounting to be distinguished from effects on sensitivity to reinforcer size. Sixteen rats received bilateral quinolinic acid-induced lesions of the AcbC; 14 received sham lesions. They were trained under a discrete-trials progressive delay schedule to press two levers (A and B) for a sucrose solution. Responses on A delivered 50 microl of the solution after a delay d(A); responses on B delivered 100 microl after d(B). d(B) increased across blocks of trials, while d(A) was manipulated across phases of the experiment. Indifference delay d(B(50)) (value of d(B) corresponding to 50% choice of B) was estimated in each phase, and linear indifference functions (d(B(50)) vs d(A)) derived. d(B(50)) increased linearly with d(A) (r(2) > 0.95 in each group). The intercept of the indifference function was lower in the lesioned than the sham-lesioned group; slope did not differ between groups. The lesioned rats had extensive neuronal loss in the AcbC. The results confirm that lesions of the AcbC promote preference for smaller, earlier reinforcers and suggest that this reflects an effect of the lesion on the rate of delay discounting.