Developing new intermuscular coordination patterns through an electromyographic signal-guided training in the upper extremity.

BACKGROUND: Muscle synergies, computationally identified intermuscular coordination patterns, have been utilized to characterize neuromuscular control and learning in humans. However, it is unclear whether it is possible to alter the existing muscle synergies or develop new ones in an intended way through a relatively short-term motor exercise in adulthood. This study aimed to test the feasibility of expanding the repertoire of intermuscular coordination patterns through an isometric, electromyographic (EMG) signal-guided exercise in the upper extremity (UE) of neurologically intact individuals. METHODS: 10 participants were trained for six weeks to induce independent control of activating a pair of elbow flexor muscles that tended to be naturally co-activated in force generation. An untrained isometric force generation task was performed to assess the effect of the training on the intermuscular coordination of the trained UE. We applied a non-negative matrix factorization on the EMG signals recorded from 12 major UE muscles during the assessment to identify the muscle synergies. In addition, the performance of training tasks and the characteristics of individual muscles' activity in both time and frequency domains were quantified as the training outcomes. RESULTS: Typically, in two weeks of the training, participants could use newly developed muscle synergies when requested to perform new, untrained motor tasks by activating their UE muscles in the trained way. Meanwhile, their habitually expressed muscle synergies, the synergistic muscle activation groups that were used before the training, were conserved throughout the entire training period. The number of muscle synergies activated for the task performance remained the same. As the new muscle synergies were developed, the neuromotor control of the trained muscles reflected in the metrics, such as the ratio between the targeted muscles, number of matched targets, and task completion time, was improved. CONCLUSION: These findings suggest that our protocol can increase the repertoire of readily available muscle synergies and improve motor control by developing the activation of new muscle coordination patterns in healthy adults within a relatively short period. Furthermore, the study shows the potential of the isometric EMG-guided protocol as a neurorehabilitation tool for aiming motor deficits induced by abnormal intermuscular coordination after neurological disorders. TRIAL REGISTRATION: This study was registered at the Clinical Research Information Service (CRiS) of the Korea National Institute of Health (KCT0005803) on 1/22/2021.

Synthetic Glabridin Derivatives Inhibit LPS-Induced Inflammation via MAPKs and NF-κB Pathways in RAW264.7 Macrophages.

Glabridin is a polyphenolic compound with reported anti-inflammatory and anti-oxidative effects. In the previous study, we synthesized glabridin derivatives-HSG4112, (S)-HSG4112, and HGR4113-based on the structure-activity relationship study of glabridin to improve its biological efficacy and chemical stability. In the present study, we investigated the anti-inflammatory effects of the glabridin derivatives in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. We found that the synthetic glabridin derivatives significantly and dose-dependently suppressed the production of nitric oxide (NO) and prostaglandin E2 (PGE2), and decreased the level of inducible nitric oxygen synthase (iNOS) and cyclooxygenase-2 (COX-2) and the expression of pro-inflammatory cytokines interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor alpha (TNF-α). The synthetic glabridin derivatives inhibited the nuclear translocation of the NF-κB by inhibiting phosphorylation of the inhibitor of κB alpha (IκB-α), and distinctively inhibited the phosphorylation of ERK, JNK, and p38 MAPKs. In addition, the compounds increased the expression of antioxidant protein heme oxygenase (HO-1) by inducing nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) through ERK and p38 MAPKs. Taken together, these results indicate that the synthetic glabridin derivatives exert strong anti-inflammatory effects in LPS-stimulated macrophages through MAPKs and NF-κB pathways, and support their development as potential therapeutics against inflammatory diseases.

Accelerated aging phenotypes in the retinal pigment epithelium of Zmpste24-deficient mice.

Age-related macular degeneration (AMD) is a chronic and progressive disease characterized by degeneration of the retinal pigment epithelium (RPE) and retina that ultimately leads to loss of vision. The pathological mechanisms of AMD are not fully known. Cellular senescence, which is a state of cell cycle arrest induced by DNA-damage or aging, is hypothesized to critically affect the pathogenesis of AMD. In this study, we examined the relationship between cellular senescence and RPE/retinal degeneration in mouse models of natural aging and accelerated aging. We performed a bulk RNA sequencing of the RPE cells from adult (8 months old) and naturally-aged old (24 months old) mice and found that common signatures of senescence and AMD pathology - inflammation, apoptosis, and blood vessel formation - are upregulated in the RPE of old mice. Next, we investigated markers of senescence and the degree of RPE/retinal degeneration in Zmpste24-deficient (Zmpste24-/-) mice, which is a model for progeria and accelerated aging. We found that Zmpste24-/- mice display markedly greater level of senescence-related markers in RPE and significant RPE/retinal degeneration compared to wild-type mice, in a manner consistent with natural aging. Overall, these results provide support for the association between cellular senescence of RPE and the pathogenesis of AMD, and suggest the use of Zmpste24-/- mice as a novel senescent RPE model of AMD.

Increasing motor cortex activation during grasping via novel robotic mirror hand therapy: a pilot fNIRS study.

BACKGROUND: Mirror therapy (MT) has been used for functional recovery of the affected hand by providing the mirrored image of the unaffected hand movement, which induces neural activation of the cortical hemisphere contralateral to the affected hand. Recently, many wearable robots assisting the movement of the hand have been developed, and several studies have proposed robotic mirror therapy (RMT) that uses a robot to provide mirrored movements of the unaffected hand to the affected hand with the robot controlled by measuring electromyography or posture of the unaffected hand. In some cases of RMT a mirror is placed to allow the person to observe only the unaffected hand but in others users simply observe the robotically assisted hand performing the mirrored movements, as was the case in this study. There have been limited evaluations of the cortical activity during RMT compared to MT and robotic therapy (RT) providing passive movements despite the difference in the modality of sensory feedback and the involvement of motor intention, respectively. METHODS: This paper analyzes bilateral motor cortex activation in nine healthy subjects and five chronic stroke survivors during a pinching task performed in MT, RT, and RMT conditions using functional near infrared spectroscopy (fNIRS). In the MT condition, the person moved the unaffected hand and observed it in a mirror while the affected hand remained still. In RT condition passive movements were provided to the affected hand with a cable-driven soft robotic glove, while, in RMT condition, the posture of the unaffected hand was measured by a sensing glove and the soft robotic glove mirrored its movement on the affected hand. RESULTS: For both groups, the RMT condition showed the greatest mean cortical activation on the motor cortex contralateral to the affected (non-dominant for the healthy group) hand compared to other conditions. Individual results indicate that RMT induces similar or greater neural activation on the motor cortex compared to MT and RT conditions. The interhemispheric activations of both groups were balanced in RMT condition. In MT condition, significantly greater activation was shown on the hemisphere ipsilateral to the affected (dominant for the healthy group) hand for both subject groups, while the contralateral side showed significantly greater activation for the healthy group in RT condition. CONCLUSION: The experimental results indicate that combining visual feedback, somatosensory feedback, and motor intention are important for greater stimulation on the contralateral motor cortex of the affected hand. RMT that includes these factors is hypothesized to achieve a more effective functional rehabilitation due to greater and more balanced cortical activation.

Intermuscular fat density as a novel prognostic factor in breast cancer patients treated with adjuvant chemotherapy.

BACKGROUND: Body composition, including sarcopenia and fat parameters, has received much attention as a prognostic factor in breast cancer. METHODS: A total of 479 breast cancer patients who underwent surgery and received adjuvant chemotherapy were enrolled in this study. Body composition, including the index and density of skeletal muscle, visceral fat, subcutaneous fat, and intermuscular fat calculated by CT scan, was used as a prognostic factor. The endpoints were breast cancer-specific survival (BCSS) and overall survival (OS). RESULTS: The number of patients with stages I, II, and III was 146 (30.5%), 237 (49.5%), and 96 (20%), respectively. Sarcopenia and muscle density were not significant prognostic factors for BCSS and OS. A high visceral fat index (VFI) was an independent prognostic factor for BCSS (HR, 2.55; 95% CI 1.10-5.95, p = 0.03) and OS (HR 2.55, 95% CI 1.26-5.16, p = 0.01). In addition, high intermuscular fat density (IMFD) was also a significant prognostic factor for BCSS (HR, 2.95; 95% CI 1.34-6.46, p = 0.007) and OS (HR 2.28, 95% CI 1.22-4.26, p = 0.01) in multivariate analysis. CONCLUSION: VFI and IMFD were significant prognostic factors for BCSS and OS in breast cancer patients treated with adjuvant chemotherapy.

Relationship between gait quality measures and modular neuromuscular control parameters in chronic post-stroke individuals.

BACKGROUND: Recent evidence suggests that disinhibition and/or hyperexcitation of the brainstem descending pathways and intraspinal motor network diffuse spastic synergistic activation patterns after stroke. This results in simplified or merged muscle sets (i.e., muscle modules or synergies) compared to non-impaired individuals and this leads to poor walking performance. However, the relations of how these neuromuscular deficits influence gait quality (e.g., symmetry or natural walking patterns) are still unclear. The objective of this exploratory study was to investigate the relations of modular neuromuscular framework and gait quality measures in chronic stroke individuals. METHODS: Sixteen chronic post-stroke individuals participated in this study. Full lower body three-dimensional kinematics and electromyography (EMG) were concurrently measured during overground walking at a comfortable speed. We first examined changes in gait quality measures across the number of muscle modules using linear regression model. Then, a stepwise multiple regression was used to investigate the optimal combination of the neuromuscular parameters that associates with gait quality measures. RESULTS: We observed that subjects who had a lower number of muscle modules revealed reduced function (i.e., speed) and greater asymmetry in the kinematic parameters including limb length, footpath area, knee flexion/extension, and hip abduction/adduction (all p < 0.05). We also found that the combination of input variables from the modular neuromuscular control framework significantly associated with gait quality measures (average [Formula: see text]). Those variables included variability accounted for ([Formula: see text]) information from the muscle modules and area under the EMG envelope curves of the quadriceps (i.e., rectus femoris and vastus lateralis) and tibialis anterior muscles. CONCLUSIONS: The results suggest that there exists a significant correlation between the neuromuscular control framework and the gait quality measures. This study helps to understand the underlying mechanism of disturbances in gait quality and provides insight for a more comprehensive outcome measure to assess gait impairment after stroke.

Alterations in intermuscular coordination underlying isokinetic exercise after a stroke and their implications on neurorehabilitation.

BACKGROUND: Abnormal intermuscular coordination limits the motor capability of stroke-affected upper limbs. By evaluating the intermuscular coordination in the affected limb under various biomechanical task constraints, the impact of a stroke on motor control can be analyzed and intermuscular coordination-based rehabilitation strategies can be developed. In this study, we investigated upper limb intermuscular coordination after a stroke during isokinetic movements. METHODS: Sixteen chronic stroke survivors and eight neurologically intact individuals were recruited. End-point forces and electromyographic activities of the shoulder and elbow muscles were measured while the participants performed isokinetic upper limb movements in a three-dimensional space. Intermuscular coordination of the stroke survivors and the control participants was quantified in the form of muscle synergies. Then, we compared the number, composition, and activation coefficients of muscle synergies and the end-point force between the groups. The correlation between the alteration of muscle synergies and the level of motor impairment was investigated. RESULTS: Four and five muscle synergies in the stroke and control groups were observed, respectively. The composition of muscle synergies was comparable between the groups, except that the three heads of the deltoid muscle were co-activated and formed one synergy in the stroke group, whereas those muscles formed two synergies in the control group. When the number of muscle synergies between the groups matched, the comparable composition of muscle synergies was observed in both groups. Alternatively, the modulation of synergy activation coefficients was altered after a stroke. The severity of motor impairments was negatively correlated with the similarity of the post-stroke synergies with respect to the mean control synergies. CONCLUSIONS: Stroke-affected upper limbs seemed to modularize the activation of the shoulder and elbow muscles in a fairly similar way to that of neurologically intact individuals during isokinetic movements. Compared with free (i.e., unconstrained) movement, exercise under biomechanical constraints including the isokinetic constraint might promote the activation of muscle synergies independently in stroke survivors. We postulated the effect of biomechanical constraints on the intermuscular coordination and suggested a possible intermuscular coordination-based rehabilitation protocol that provides the biomechanical constraint appropriate to a trainee throughout the progress of rehabilitation.

Improved cortical activity and reduced gait asymmetry during poststroke self-paced walking rehabilitation.

BACKGROUND: For patients with gait impairment due to neurological disorders, body weight-supported treadmill training (BWSTT) has been widely used for gait rehabilitation. On a conventional (passive) treadmill that runs at a constant speed, however, the level of patient engagement and cortical activity decreased compared with gait training on the ground. To increase the level of cognitive engagement and brain activity during gait rehabilitation, a self-paced (active) treadmill is introduced to allow patients to actively control walking speed, as with overground walking. METHODS: To validate the effects of self-paced treadmill walking on cortical activities, this paper presents a clinical test with stroke survivors. We hypothesized that cortical activities on the affected side of the brain would also increase during active walking because patients have to match the target walking speed with the affected lower limbs. Thus, asymmetric gait patterns such as limping or hobbling might also decrease during active walking. RESULTS: Although the clinical test was conducted in a short period, the patients showed higher cognitive engagement, improved brain activities assessed by electroencephalography (EEG), and decreased gait asymmetry with the self-paced treadmill. As expected, increases in the spectral power of the low γ and ß bands in the prefrontal cortex (PFC), premotor cortex (PMC), and supramarginal gyrus (SG) were found, which are possibly related to processing sensory data and planning voluntary movements. In addition, these changes in cortical activities were also found with the affected lower limbs during the swing phase. Since our treadmill controller tracked the swing speed of the leg to control walking speed, such results imply that subjects made substantial effort to control their affected legs in the swing phase to match the target walking speed. CONCLUSIONS: The patients also showed reduced gait asymmetry patterns. Based on the results, the self-paced gait training system has the potential to train the symmetric gait and to promote the related cortical activities after stroke. Trial registration Not applicable.

Differences in the Efficacies of Pazopanib and Gemcitabine/Docetaxel as Second-Line Treatments for Metastatic Soft Tissue Sarcoma.

BACKGROUND: We retrospectively investigated the treatment outcomes of second-line treatment with pazopanib or gemcitabine/docetaxel in patients with advanced soft tissue sarcoma (STS). METHODS: Ninety-one patients who were treated with pazopanib or gemcitabine/docetaxel for advanced STS between 1995 and 2015 were analyzed. RESULTS: Forty-six and 45 patients received pazopanib and gemcitabine/docetaxel, respectively. The median progression-free survival for the group treated with pazopanib was 4.5 months compared with 3.0 months for the gemcitabine/docetaxel group (p = 0.593). The median overall survival for the group treated with pazopanib was 12.6 months compared with 14.2 months for the gemcitabine/docetaxel group (p = 0.362). The overall response rates (ORRs) were 6.5 and 26.7% in the pazopanib and gemcitabine/docetaxel groups, respectively. The following parameters had ORRs favoring gemcitabine/docetaxel: age ≥50 years (31.6 vs. 2.9%, p = 0.006), histologic grade 1-2 (40.9 vs. 0%, p = 0.001), and poor first-line treatment response (23.3 vs. 3.0%, p = 0.022). Gemcitabine/docetaxel was associated with better ORRs for the following histologic subtypes: leiomyosarcoma (p = 0.624), malignant fibrous histiocytoma/undifferentiated pleomorphic sarcoma (p = 0.055), and angiosarcoma (p = 0.182). However, the ORR of synovial sarcoma favored pazopanib (p = 0.99). CONCLUSIONS: The efficacies of pazopanib and gemcitabine/docetaxel as second-line treatments after doxorubicin or ifosfamide failure differed among clinical and histologic subgroups and appeared to facilitate a more personalized treatment approach for advanced STS.

Artificial Neural Network Learns Clinical Assessment of Spasticity in Modified Ashworth Scale.

OBJECTIVE: To propose an artificial intelligence (AI)-based decision-making rule in modified Ashworth scale (MAS) that draws maximum agreement from multiple human raters and to analyze how various biomechanical parameters affect scores in MAS. DESIGN: Prospective observational study. SETTING: Two university hospitals. PARTICIPANTS: Hemiplegic adults with elbow flexor spasticity due to acquired brain injury (N=34). INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Twenty-eight rehabilitation doctors and occupational therapists examined MAS of elbow flexors in 34 subjects with hemiplegia due to acquired brain injury while the MAS score and biomechanical data (ie, joint motion and resistance) were collected. Nine biomechanical parameters that quantify spastic response described by the joint motion and resistance were calculated. An AI algorithm (or artificial neural network) was trained to predict the MAS score from the parameters. Afterwards, the contribution of each parameter for determining MAS scores was analyzed. RESULTS: The trained AI agreed with the human raters for the majority (82.2%, Cohen's kappa=0.743) of data. The MAS scores chosen by the AI and human raters showed a strong correlation (correlation coefficient=0.825). Each biomechanical parameter contributed differently to the different MAS scores. Overall, angle of catch, maximum stretching speed, and maximum resistance were the most relevant parameters that affected the AI decision. CONCLUSIONS: AI can successfully learn clinical assessment of spasticity with good agreement with multiple human raters. In addition, we could analyze which factors of spastic response are considered important by the human raters in assessing spasticity by observing how AI learns the expert decision. It should be noted that few data were collected for MAS3; the results and analysis related to MAS3 therefore have limited supporting evidence.

Marked Loss of Muscle, Visceral Fat, or Subcutaneous Fat After Gastrectomy Predicts Poor Survival in Advanced Gastric Cancer: Single-Center Study from the CLASSIC Trial.

BACKGROUND: There is increasing interest in the influence of body composition on oncological outcomes. We evaluated the role of skeletal muscle and fat among patients with gastric cancer (GC) who underwent gastrectomy with or without adjuvant chemotherapy, as well as those changes' associations with survival outcomes. METHODS: The present study evaluated 136 patients with GC who were enrolled in the CLASSIC Trial at Yonsei Cancer Center. Baseline body compositions including skeletal muscle area, Hounsfield units (HU), visceral fat area, and subcutaneous fat area were measured by preoperative computed tomography (CT). CT before and after the gastrectomy were used to determine the 6-month relative changes in body composition parameters. Continuous variables were dichotomized according to the best cutoff values by Contal and O'Quigley method. RESULTS: Seventy-three patients (53.7%) underwent surgery alone, and 63 patients (46.3%) underwent surgery followed by adjuvant chemotherapy. The baseline body composition parameters were not associated with disease-free survival (DFS) or overall survival (OS). Except for the HU, the marked loss of muscle, visceral fat, or subcutaneous fat significantly predicted shorter DFS and OS. Patients with a marked loss in at least one significant body composition parameter had significantly shorter DFS (hazard ratio 2.9, 95% confidence interval 1.7-4.8, P < 0.001) and OS (hazard ratio 2.9, 95% confidence interval 1.7-5.0, P < 0.001). CONCLUSIONS: Marked loss in body composition parameters significantly predicted shorter DFS and OS among patients with GC who underwent gastrectomy. Postoperative nutrition and active healthcare interventions could improve the prognosis of these GC patients.

Technical development of transcutaneous electrical nerve inhibition using medium-frequency alternating current.

BACKGROUND: Innovative technical approaches to controlling undesired sensory and motor activity, such as hyperalgesia or spasticity, may contribute to rehabilitation techniques for improving neural plasticity in patients with neurologic disorders. To date, transcutaneous electrical stimulation has used low frequency pulsed currents for sensory inhibition and muscle activation. Yet, few studies have attempted to achieve motor nerve inhibition using transcutaneous electrical stimulation. This study aimed to develop a technique for transcutaneous electrical nerve inhibition (TENI) using medium-frequency alternating current (MFAC) to suppress both sensory and motor nerve activity in humans. METHODS: Surface electrodes were affixed to the skin of eight young adults to stimulate the median nerve. Stimulation intensity was increased up to 50% and 100% of the pain threshold. To identify changes in sensory perception by transcutaneous MFAC (tMFAC) stimulation, we examined tactile and pressure pain thresholds in the index and middle fingers before and after stimulation at 10 kHz. To demonstrate the effect of tMFAC stimulation on motor inhibition, stimulation was applied while participants produced flexion forces with the index and middle fingers at target forces (50% and 90% of MVC, maximum voluntary contraction). RESULTS: tMFAC stimulation intensity significantly increased tactile and pressure pain thresholds, indicating decreased sensory perception. During the force production task, tMFAC stimulation with the maximum intensity immediately reduced finger forces by ~ 40%. Finger forces recovered immediately after stimulation cessation. The effect on motor inhibition was greater with the higher target force (90% MVC) than with the lower target (50% MVC). Also, higher tMFAC stimulation intensity provided a greater inhibition effect on both sensory and motor nerve activity. CONCLUSION: We found that tMFAC stimulation immediately inhibits sensory and motor activity. This pre-clinical study demonstrates a novel technique for TENI using MFAC stimulation and showed that it can effectively inhibit both sensory perception and motor activity. The proposed technique can be combined with existing rehabilitation devices (e.g., a robotic exoskeleton) to inhibit undesired sensorimotor activities and to accelerate recovery after neurologic injury.

ANO9/TMEM16J promotes tumourigenesis via EGFR and is a novel therapeutic target for pancreatic cancer.

BACKGROUND: Anoctamin (ANO)/transmembrane member 16 (TMEM16) proteins mediate diverse physiological and pathophysiological functions including cancer cell proliferation. The present study aimed to identify the role of ANOs in pancreatic cancer. METHODS: In an initial screen of ANOs, ANO9/TMEM16J was overexpressed in pancreatic cancer cells, and its role in the pathogenesis of pancreatic cancer was evaluated using an integrated in vitro and in vivo approach. To determine clinical relevance of the experimental findings, the prognostic value of ANO9 was evaluated in patients with pancreatic cancer. RESULTS: The ANO9 mRNA and protein levels were increased in pancreatic cancer-derived cells. Exogenous expression of ANO9 in PANC-1 cells significantly increased cell proliferation in cell cultures and in mice. In contrast, knockdown of ANO9 in AsPC-1, BxPC-3, and Capan-2 cells strongly inhibited cell proliferation. Mechanistic analysis suggested that physical association of ANO9 with epidermal growth factor receptor (EGFR) underlies ANO9-induced cell proliferation. Knockdown of ANO9 augmented the effects of the EGFR inhibitor and the cytotoxic agent on pancreatic cancer cell proliferation. In addition, high ANO9 expression is a poor prognostic factor in patients with pancreatic cancer. CONCLUSIONS: The ANO9/TMEM16J appears to be a clinically useful prognostic marker for pancreatic cancer and a potential therapeutic target.

Effects of hormone receptor status on the durable response of trastuzumab-based therapy in metastatic breast cancer.

PURPOSE: Trastuzumab-based treatment is the standard care for patients with HER2+ metastatic breast cancer (MBC). About 10% of HER2+ MBC showed a long-term durable response (progression-free survival, PFS > 3 years) to trastuzumab-based therapy. The aim of this study is to identify clinico-pathologic factors for a durable response to trastuzumab-based therapy in HER2-positive MBC. METHODS: In the Yonsei Breast Cancer MBC Database, we identified 1218 MBC patients who were diagnosed from 2006 to 2015. Among them, 294 had HER2+ disease, and 153 received trastuzumab plus taxane chemotherapy as first-line treatment. Clinico-pathologic factors, such as hormone receptor (HR) status and metastatic sites, were reviewed. To evaluate a durable response, landmark analysis was performed. RESULTS: The median follow-up time was 28 months (95% CI 4.4-83.0 months). Of 153 HER2+ patients, there were 73 HR- patients (47.7%), and bone was the most common metastatic site. The median PFS and overall survival (OS) were 12 and 39 months, respectively. HR- patients showed a tendency toward longer PFS (median, 13 vs. 11 months, P = 0.160) compared with HR+ patients. Patients with non-visceral metastases had longer median PFS and OS than those with visceral disease (median PFS, 15 vs. 11 months, P = 0.012; median OS, 75 vs. 34 months, P = 0.03). Landmark analysis at 9 months suggested that the PFS of HR- patients was significantly longer than that of HR+ patients (median, 19 vs. 9 months, P = 0.008). CONCLUSIONS: Among patients with HER2+ MBC, HR status is a possible predictive biomarker of a durable response to trastuzumab-based therapy.

Role of adjuvant chemotherapy in locally advanced rectal cancer with ypT0-3N0 after preoperative chemoradiation therapy and surgery.

BACKGROUND: We aimed to explore the clinical benefit of adjuvant chemotherapy (AC) with fluoropyrimidine in patients with ypT0-3N0 rectal cancer after preoperative chemoradiation therapy (CRT) followed by total mesorectal excision (TME). METHODS: Patients with ypT0-3N0 rectal cancer after preoperative CRT and TME were included using prospectively collected tumor registry cohort between January 2001 and December 2013. Patients were categorized into two groups according to the receipt of AC. Disease-free survival (DFS) and overall survival (OS) were compared between the adjuvant and observation groups. To control for potential confounding factors, we also calculated propensity scores and performed propensity score-matched analysis for DFS and OS. RESULTS: Of the 339 evaluated patients, 87 patients (25.7%) did not receive AC. There were no differences in DFS (hazard ratio [HR], 0.921; 95% confidence interval [CI], 0.562-1.507; P = 0.742) and OS (HR, 0.835; 95% CI, 0.423-1.648; P = 0.603) between the adjuvant and observation groups. After propensity score matching, DFS (HR, 1.129; 95% CI, 0.626-2.035; P = 0.688) and OS (HR, 1.200; 95% CI, 0.539-2.669; P = 0.655) did not differ between the adjuvant and observation groups. Advanced T stage and positive resection margin were independently associated with inferior DFS and OS on multivariate analysis. CONCLUSIONS: AC did not improve DFS and OS for patients with ypT0-3N0 rectal cancer after preoperative CRT followed by TME in this cohort study. The confirmative role of AC in locally advanced rectal cancer should be evaluated in prospective randomized trials with a larger sample size.

Examining impairment of adaptive compensation for stabilizing motor repetitions in stroke survivors.

The hand, one of the most versatile but mechanically redundant parts of the human body, suffers more and longer than other body parts after stroke. One of the rehabilitation paradigms, task-oriented rehabilitation, encourages motor repeatability, the ability to produce similar motor performance over repetitions through compensatory strategies while taking advantage of the motor system's redundancy. The previous studies showed that stroke survivors inconsistently performed a given motor task with limited motor solutions. We hypothesized that stroke survivors would exhibit deficits in motor repeatability and adaptive compensation compared to healthy controls in during repetitive force-pulse (RFP) production tasks using multiple fingers. Seventeen hemiparetic stroke survivors and seven healthy controls were asked to repeatedly press force sensors as fast as possible using the four fingers of each hand. The hierarchical variability decomposition model was employed to compute motor repeatability and adaptive compensation across finger-force impulses, respectively. Stroke survivors showed decreased repeatability and adaptive compensation of force impulses between individual fingers as compared to the control (p < 0.05). The stroke survivors also showed decreased pulse frequency and greater peak-to-peak time variance than the control (p < 0.05). Force-related variables, such as mean peak force and peak force interval variability, demonstrated no significant difference between groups. Our findings indicate that stroke-induced brain injury negatively affects their ability to exploit their redundant or abundant motor system in an RFP task.

Effects of microsatellite instability on recurrence patterns and outcomes in colorectal cancers.

BACKGROUND: Among colorectal cancers (CRCs), high-frequency microsatellite instability (MSI-H) is associated with a better prognosis, compared with low-frequency MSI or microsatellite stability (MSI-L/MSS). However, it is unclear whether MSI affects the prognosis of recurrent CRCs. METHODS: This study included 2940 patients with stage I-III CRC who underwent complete resection. The associations of MSI status with recurrence patterns, disease-free survival (DFS), overall survival from diagnosis to death (OS1), and overall survival from recurrence to death (OS2) were analysed. RESULTS: A total of 261 patients (8.9%) had MSI-H CRC. Patients with MSI-H CRC had better DFS, compared to patients with MSI-L/MSS CRC (hazard ratio (HR): 0.619, P<0.001). High-frequency microsatellite instability CRC was associated with more frequent local recurrence (30.0% vs 12.0%, P=0.032) or peritoneal metastasis (40.0% vs 12.3%, P=0.003), and less frequent lung (10.0% vs 42.5%, P=0.004) or liver metastases (15.0% vs 44.7%, P=0.01). Recurrent MSI-H CRC was associated with worse OS1 (HR: 1.363, P=0.035) and OS2 (HR: 2.667, P<0.001). An analysis of patients with colon cancer yielded similar results. CONCLUSIONS: Recurrence patterns differed between MSI-H CRC and MSI-L/MSS CRC, and recurrent MSI-H CRCs had a worse prognosis.

Pharmacogenetic analysis of advanced non-small-cell lung cancer patients treated with first-line paclitaxel and carboplatin chemotherapy.

BACKGROUND: Genetic polymorphisms contribute toward interindividual variations in drug response. We investigated the effects of genetic polymorphisms on the clinical outcome of advanced non-small-cell lung cancer patients with first-line paclitaxel and carboplatin. MATERIALS AND METHODS: A total of 194 non-small-cell lung cancer patients were prospectively enrolled from January 2010 to January 2013. We genotyped 11 polymorphisms in seven genes involved in the glycolysis pathway and the related pharmacokinetic/pharmacodynamic pathway. Genetic associations with PET-SUV, survival outcome, and toxicity were analyzed, and in-vitro drug transport activity was measured in the oocyte system. RESULTS: Patients with the c.334 T>G and c.699 G>A homozygous variant in SLCO1B3 showed a higher incidence of grade 3/4 anemia (P=0.002). Transport activities of oocyte that overexpress the SLCO1B3 c.699 G>A variant showed a significantly decreased uptake of paclitaxel compared with the wild-type expressing oocytes. In addition, patients with GG/GA/AA genotypes of ABCB1, c.2677 T>G/A locus showed inferior progression-free survival (hazard ratio=1.49, P=0.017) compared with other genotypes. The GA genotype of HIF1A, c.1834 G>A locus was associated with inferior progression-free survival compared with the GG genotype (hazard ratio=2.47, P=0.008). CONCLUSION: This study showed that the SLCO1B3 c.699 G>A polymorphism may predict anemia and ABCB1, HIF1A polymorphism are highly predictive for worse survival in advanced NSCLC with first-line paclitaxel and carboplatin.

Benefit of Adjuvant Chemotherapy After Curative Resection of Lung Metastasis in Colorectal Cancer.

BACKGROUND: The survival benefit of adjuvant chemotherapy after colorectal cancer (CRC) lung metastasectomy is uncertain. METHODS: We enrolled 221 CRC patients who underwent pulmonary metastasectomy between October 2002 and July 2013, including those with previous liver metastasis that had been curatively resected. Disease-free survival (DFS) and overall survival (OS) were calculated from the day of lung metastasectomy. RESULTS: Among all patients, 176 (79.6%) received adjuvant chemotherapy after lung metastasectomy. Median follow-up was 34.7 months from the time of lung metastasectomy [95% confidence interval (95% CI), 7.4-90.9 months]. Patients treated with adjuvant chemotherapy had longer DFS compared with surgery alone (median 32.7 vs 11.2 months respectively, P = 0.076). Multivariate analysis revealed previous liver metastasis, preoperative carcinoembryonic antigen ≥5 ng/mL, disease-free interval <24 months, and surgery without adjuvant chemotherapy as independent risk factors for recurrence. Low-risk patients who had 0-1 risk factors received a significant survival benefit from adjuvant chemotherapy [hazard ratio (HR) 0.54; 95% CI 0.32-0.91, P = 0.020]; however, high-risk patients with ≥2 risk factors did not (HR 1.02; 95% CI 0.48-2.14, P = 0.964). Patients treated with adjuvant chemotherapy showed no OS benefit compared with patients who received surgery alone (median 89.6 vs 86.8 months respectively, P = 0.833). CONCLUSIONS: CRC patients received lung metastasectomy could have a DFS benefit from adjuvant chemotherapy, especially in low-risk patients. Larger, prospective studies are needed to evaluate the role of adjuvant chemotherapy after CRC lung metastasectomy.

Improving Kinematic Accuracy of Soft Wearable Data Gloves by Optimizing Sensor Locations.

Bending sensors enable compact, wearable designs when used for measuring hand configurations in data gloves. While existing data gloves can accurately measure angular displacement of the finger and distal thumb joints, accurate measurement of thumb carpometacarpal (CMC) joint movements remains challenging due to crosstalk between the multi-sensor outputs required to measure the degrees of freedom (DOF). To properly measure CMC-joint configurations, sensor locations that minimize sensor crosstalk must be identified. This paper presents a novel approach to identifying optimal sensor locations. Three-dimensional hand surface data from ten subjects was collected in multiple thumb postures with varied CMC-joint flexion and abduction angles. For each posture, scanned CMC-joint contours were used to estimate CMC-joint flexion and abduction angles by varying the positions and orientations of two bending sensors. Optimal sensor locations were estimated by the least squares method, which minimized the difference between the true CMC-joint angles and the joint angle estimates. Finally, the resultant optimal sensor locations were experimentally validated. Placing sensors at the optimal locations, CMC-joint angle measurement accuracies improved (flexion, 2.8° ± 1.9°; abduction, 1.9° ± 1.2°). The proposed method for improving the accuracy of the sensing system can be extended to other types of soft wearable measurement devices.