Wearables have been applied in the field of fitness in recent years to monitor human muscles by recording electromyographic (EMG) signals. Understanding muscle activation during exercise routines ...allows strength athletes to achieve the best results. Hydrogels, which are widely used as wet electrodes in the fitness field, are not an option for wearable devices due to their characteristics of being disposable and skin-adhesion. Therefore, a lot of research has been conducted on the development of dry electrodes that can replace hydrogels. In this study, to make it wearable, neoprene was impregnated with high-purity SWCNTs to develop a dry electrode with less noise than hydrogel. Due to the impact of COVID-19, the demand for workouts to improve muscle strength, such as home gyms and personal trainers (PT), has increased. Although there are many studies related to aerobic exercise, there is a lack of wearable devices that can assist in improving muscle strength. This pilot study proposed the development of a wearable device in the form of an arm sleeve that can monitor muscle activity by recording EMG signals of the arm using nine textile-based sensors. In addition, some machine learning models were used to classify three arm target movements such as wrist curl, biceps curl, and dumbbell kickback from the EMG signals recorded by fiber-based sensors. The results obtained show that the EMG signal recorded by the proposed electrode contains less noise compared to that collected by the wet electrode. This was also evidenced by the high accuracy of the classification model used to classify the three arms workouts. This work classification device is an essential step towards wearable devices that can replace next-generation PT.
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of complex etiology that primarily affects women of childbearing age. The development of SLE is attributed to the breach of ...immunological tolerance and the interaction between SLE-susceptibility genes and various environmental factors, resulting in the production of pathogenic autoantibodies. Working in concert with the innate and adaptive arms of the immune system, lupus-related autoantibodies mediate immune-complex deposition in various tissues and organs, leading to acute and chronic inflammation and consequent end-organ damage. Over the past two decades or so, the impact of genetic susceptibility on the development of SLE has been well demonstrated in a number of large-scale genetic association studies which have uncovered a large fraction of genetic heritability of SLE by recognizing about a hundred SLE-susceptibility loci. Integration of genetic variant data with various omics data such as transcriptomic and epigenomic data potentially provides a unique opportunity to further understand the roles of SLE risk variants in regulating the molecular phenotypes by various disease-relevant cell types and in shaping the immune systems with high inter-individual variances in disease susceptibility. In this review, the catalogue of SLE susceptibility loci will be updated, and biological signatures implicated by the SLE-risk variants will be critically discussed. It is optimistically hoped that identification of SLE risk variants will enable the prognostic and therapeutic biomarker armamentarium of SLE to be strengthened, a major leap towards precision medicine in the management of the condition.
Objective
Several clinical trials aimed at treating various autoimmune diseases, including systemic lupus erythematosus (SLE), by introducing mesenchymal stem cells (MSCs) have been conducted. ...However, with refractory lupus nephritis (LN), the outcomes of MSC transplantation are not well known, and further validation is required. In particular, data concerning the safety and efficacy of LN treatment using bone marrow-derived MSCs (BM-MSCs) are still lacking.
Methods
We identified characteristics of BM-MSCs in terms of cell morphology, chromosomal stability, differentiation capacity, and phenotype through cell passages. The in vivo stability of BM-MSCs was evaluated by single-dose and repeated-dose toxicity tests, tumorigenicity tests, and biodistribution tests using lupus mouse models. Based on the encouraging nonclinical results, we conducted a nonrandomized, open-label, single-arm phase I clinical trial to evaluate the tolerability and safety of a single administration of haploidentical allogeneic BM-MSCs (CS20AT04) in seven LN patients (NCT03174587). We used a classical three + three design to find the optimal dosage. The starting dose was 2.0×106 cells/kg and escalated to 3.0×106 cells/kg if there was no dose-limiting toxicity (DLT). Evaluation of the safety and tolerability was assessed 28 days after the infusion, and the maximum tolerated dose was determined.
Results
Properly cultured BM-MSCs showed high proliferation and multipotency, but chromosomal changes were not found. There were two deaths by a rapid administration rate in the high-dose group (2.0×106 cells/head) in a single administration test. BM-MSCs were distributed in the kidneys until Day 7. In the phase I clinical trial, seven LN patients were enrolled. Participants received BM-MSCs through intravenous infusion. There was no DLT at both initial dose (2.0×106 cells/kg) and escalated dose (3.0×106 cells/kg). One patient was not administered the full 2.0×106 cells/kg dose because of a technical error during infusion. This patient did not show DLT. Three adverse events were reported, namely, one diarrhea, one toothache, and one arthralgia, and all were considered NCI-CTC grade I events.
Conclusion
We defined the characteristics of BM-MSCs and identified their safety and tolerability in both animal models and a phase I clinical trial. The maximum tolerated dose was determined to be 3.0×106 cells/kg in patients with LN.
A single cycle (two repeated treatments) with intrathecal autologous bone marrow-derived mesenchymal stem cells (BM-MSCs, 26-day interval) showed safety and provided therapeutic benefit lasting 6 ...months in patients with ALS but did not demonstrate long-term efficacy. This phase III clinical trial (ALSUMMIT) protocol was developed to evaluate the long-term efficacy and safety of the combined protocol of single-cycle intrathecal therapy and three additional booster injections of BM-MSC (Lenzumestrocel) treatment in patients with ALS.
ALSUMMIT is a multicentre, randomized, double-blind, parallel-group, sham procedure-controlled, phase III trial for ALS. The 115 subjects will be randomized (1:2:2) into three groups: (1) study Group 1 (single-cycle, two repeated injections with 26-day interval), (2) study Group 2 (single-cycle + three additional booster injections at 4, 7, and 10 months), and (3) the control group. Participants who have an intermediate rate of disease progression will be included in this trial to reduce clinical heterogeneity. The primary endpoint will be evaluated by combined assessment of function and survival (CAFS), also known as joint rank scores (JRS), at 6 months (study Group 1 vs. control) and 12 months (study Group 2 vs. control) after the first Lenzumestrocel or placebo administration. Safety assessment will be performed throughout the study period. Additionally, after the 56-week main study, a long-term follow-up observational study will be conducted to evaluate the long-term efficacy and safety up to 36 months.
Lenzumestrocel is the orphan cell therapy product for ALS conditionally approved by the South Korea Ministry of Food and Drug Safety (MFDS). This ALSUMMIT protocol was developed for the adoption of enrichment enrolment, add-on design, and consideration of ethical issues for the placebo group.
ClinicalTrials.gov NCT04745299 . Registered on Feb 9, 2021. Clinical Research Information Service (CRIS) KCT0005954 . Registered on Mar 4, 2021.
Neuronata-R® (lenzumestrocel) is an autologous bone marrow-derived mesenchymal stem cell (BM-MSC) product, which was conditionally approved by the Korean Ministry of Food and Drug Safety (KMFDS, ...Republic of Korea) in 2013 for the treatment of amyotrophic lateral sclerosis (ALS). In the present study, we aimed to investigate the long-term survival benefits of treatment with intrathecal lenzumestrocel.
A total of 157 participants who received lenzumestrocel and whose symptom duration was less than 2 years were included in the analysis (BM-MSC group). The survival data of placebo participants from the Pooled-Resource Open-Access ALS Clinical Trials (PROACT) database were used as the external control, and propensity score matching (PSM) was used to reduce confounding biases in baseline characteristics. Adverse events were recorded during the entire follow-up period after the first treatment.
Survival probability was significantly higher in the BM-MSC group compared to the external control group from the PROACT database (log-rank,
< 0.001). Multivariate Cox proportional hazard analysis showed a significantly lower hazard ratio for death in the BM-MSC group and indicated that multiple injections were more effective. Additionally, there were no serious adverse drug reactions found during the safety assessment, lasting a year after the first administration.
The results of the present study showed that lenzumestrocel treatment had a long-term survival benefit in real-world ALS patients.
Background The antinuclear antibody (ANA)-positive asymptomatic individuals are at higher risk of developing systemic lupus erythematosus (SLE). However, the genetic burden for SLE in preclinical ...ANA-positive phase remains largely unknown. In this study, we analyzed SLE-specific polygenic risk scores (PRSs) from a prospective cohort comprising Korean individuals with preclinical autoantibodies, SLE, or none of these conditions to understand the effect of SLE-risk genetic variants on the development of ANA. Methods The PRS for SLE was calculated from genome-wide variants data obtained from 349 individuals with preclinical autoimmunity, 2,057 patients with SLE, and 33,596 healthy controls based on the known risk effects of 180 SLE-risk variants. Preclinical autoantibodies-positive individuals who were diagnosed by rheumatologists, tested positive for at least one among ANA, rheumatoid factor (RF), or anti-cyclic citrullinated peptide autoantibody (anti-CCP). Differences in PRSs among phenotypic groups were assessed using ANOVA with adjustment for genotypic principal components and sex while controlling for the family-wise error rate. Results There was a significant increase in the SLE PRS in the preclinical ANA-positive group (ANA titers ≥ 1:160) compared to healthy controls (p=2.69x10−5) and the preclinical ANA-negative group with preclinical autoimmunity (positive for RF or anti-CCP) (p=2.42x10−²), although their SLE genetic burden was significantly weaker than patients with SLE (p=7.48x10−²5). In addition, SLE PRSs were gradually increased according to the level of ANA titers in a stratified analysis (p=2.38x10−³, figure 1). In contrast, the presence of anti-CCP autoantibodies (irrelevant to SLE) in the preclinical stage was not associated with high SLE PRSs. Conclusions This study demonstrated that the genetic burden for SLE contributes to the preclinical development of ANA. Abstract LO-042 Figure 1 Polygenic risk scores (PRSs) for SLE were plotted based on the following phenotypes: healthy controls, preclinical autoimmunity, and SLE. The individuals with preclinical autoimmunity were divided into four groups according to antinuclear antibody (ANA) titers Figure omitted. See PDF
Resistance training is becoming increasingly important and widespread. Decomposition of the muscle loads applied is important for injury prevention and determining the load on the targeted muscles. ...In this study, a flexible textile PET (polyethylene terephthalate)/SP(Spandex) SWCNT (Single-walled carbon nanotube) stretch sensor was fabricated and attached at four locations: the elbow, brachioradialis/flexor carpi radialis, biceps brachii, and triceps brachii. The stretch sensors attached to the elbow can measure the angle of elbow flexion without an IMU 9-axis sensor using quadratic fitting. A Multi-Layer Perceptron (MLP) was used to decompose the muscle volume expansions of the 3muscle by angle. The model provided a good fit for all three muscles, with R-squared values ranging from Test set 0.98725 to 0.99815. Through one input and three ouput fitting, the muscle volume expansion quantities during the bicep barbell curl were decomposed and compared with data. The results showed that the brachioradialis/flexor carpi radialis muscle maintained 13% of the arm muscle volume up to 60°, then increased to 44% at 100°. The biceps brachii muscle steadily increased to 70% from 0° up to 60°, and then maintained 40% at 100° due to the volume increase of other muscles. The triceps brachii muscle maintained 9% of the arm muscle volume up to 90°, then increased to 20% at 100°. This study shows that muscle volume expansion can be easily measured with a non-body contact wearable device, unlike many existing contact methods for measuring muscle activity like EMG (electro-myography), etc. This study provides a novel approach for easily measuring muscle volume expansion and decomposition in wearable devices, which can indirectly indicate injury prevention and muscle loading in target areas through balance optimization among local muscles.
Structural variations such as copy number variations (CNVs) have a functional impact on various human traits. This study profiled genome-wide CNVs in Korean patients with rheumatoid arthritis (RA) to ...investigate the efficacy of treatment with TNF-α blockers.
A total of 357 Korean patients with RA were examined for the efficacy of TNF-α blocker treatment. Disease activity indexes were measured at baseline and 6 months after the treatment. The patients were classified as responders and non-responders based on the change in disease activity indexes according to the EULAR response criteria. CNVs in the same patients were profiled using fluorescence signal intensity data generated by a genome-wide SNP array. The association of CNVs with response to TNF-α blockers was analyzed by multivariate logistic regression accounting for genetic background and clinical factors including body mass index, gender, baseline disease activity, TNF-α blocker used, and methotrexate treatment.
The study subjects varied in their responses to TNF-α blockers and had 286 common CNVs in autosomes. We identified that the 3.8-kb deletion at 2q14.3 in 5% of the subjects was associated with response to TNF-α blockers (1.37 × 10
≤ P ≤ 4.07 × 10
) at a false discovery rate threshold of 5%. The deletion in the identified CNV was significantly more frequent in the non-responders than in the responders, indicating worse response to TNF-α blockers in the deletion carriers. The 3.8-kb deletion at 2q14.3 is located in an intergenic region with the binding sites of two transcription factors, MAFF and MAFK.
This study obtained the CNV landscape of Korean patients with RA and identified the common regional deletion associated with poor response to treatment with TNF-α blockers.
In this study, the authors proposed a method to fabricate a resistive stretch textile sensor from polyester spandex (PET/SP) fabric and commercial single-walled carbon nanotube (SWCNT). In addition, ...we designed and trained a one-dimension convolutional neural network to classify four resistance workouts, which employed data acquired from the proposed sensor as the input. To figure out the most appropriate PET/SP sample for the deep learning application, we investigated morphologies and characterization of three samples in distinct conditions of the coating process. Data acquired from the proposed sensor illustrated the significant difference between activated and non-activated muscle groups in each specific exercise. With the PET/SP sample which met the requirements of the application, after 100 epochs, the deep learning model achieved 97.2% training accuracy and 90% test accuracy. This study demonstrates that the SWCNT-coated PET/SP stretch textile sensor can be utilized effectively to track the activity of forearm muscles during resistance training. Other than that, the proposed 1D-CNN, with the advantage of training time and computational cost, is able to classify time series data with high performance and thus can be applied widely in various deep learning applications, especially in the healthcare and sports industries.
This study proposes the use of a CNN model to predict the resistance of conductive fabrics by utilizing the brightness information from their images, aiming to address the limitations of traditional ...contact-based measurement methods and explore the feasibility of non-contact resistance measurement. Conductive fabrics were produced using environmentally friendly cellulose fiber as a base material, with a dip-coating and padding process involving water-based single-walled carbon nanotube (SWCNT). After scanning the produced conductive fabrics and meticulously preprocessing the images, a dataset for CNN training was constructed, comprising label values corresponding to the sheet resistance of each image. ANOVA analysis confirmed a statistically significant relationship ( p-value = 8.04145e^-18) between the brightness of conductive fabric images and their sheet resistance. By leveraging the relationship between the brightness of fabric images and sheet resistance, training of the CNN model yielded an RMSE of 0.0558 and an R-squared value of 0.9557, validating the effectiveness of the designed CNN model for image-based resistance prediction. This research is expected to contribute to the development of future real-time monitoring and control systems, providing a crucial foundation for the advancement of data-driven measurement and control systems based on computer vision and machine learning techniques. Furthermore, it is anticipated to unveil new possibilities for various applications of conductive fabrics.
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