Tele-rehabilitation in COVID-19 survivors (TERCOV): An investigator-initiated, prospective, multi-center, real-world study.

INTRODUCTION: Center-based rehabilitation is limited by COVID-19 infectivity and social distancing policy. We hypothesized that discharged patients benefit from 8-week home-based tele-rehabilitation (tele-PR) using mobile phones and low-cost instruments. METHODS: The TERCOV (Tele-rehabilitation in COVID-19 survivors) is an investigator-initiated, prospective, multi-center, real-world study. After proper assessment, 186 discharge patients received tele-PR by smartphone, including breathing exercise, respiratory muscle training, aerobic exercise, and resistance training. Physicians, physiotherapists, and nurses provided guidance through smartphone applications. The primary outcome was six-minute walk distance (6MWD). The secondary outcomes included hand grip, short physical performance battery, maximal inspiratory pressure, maximal expiratory pressure, self-rating anxiety/depression scale (SAS/SDS), 36-item short-form health survey (SF-36) and international physical activity questionnaire. RESULTS: Dyspnea subgroups were more functionally impaired. After tele-PR, improvements were observed in exercise capacity(∆6MWD: 16.80 m, 95% CI 1.18-32.42, p < 0.0001), limb muscle function (∆SPPB 0.25 points, 95% CI 0.05-0.46), respiratory muscle strength (∆MIP 16.50 cm H2O, 95% CI 9.22-23.78, p < 0.0001; ∆MEP: 12.09 cm H2O, 95% CI 3.48-20.70, p = 0.0002), health-related quality of life (∆SF-36 49.85, 95% CI: 21.01-78.69, p < 0.0001), physical activity(∆HEPA 13.01%, p = 0.0029). Anxiety reduced in patients with mMRC ≥ 2 (∆SAS = -4.19 points, CI -8.16 to -0.22, p = 0.03). Greater change was seen in dyspnea patients. IMPLICATIONS ON PHYSIOTHERAPY PRACTICE: Supervised/semi-supervised tele-PR is a promising option during the pandemic. Patients with Dyspnea benefit more.

A new stress measurement strategy based on time-frequency characteristics of Lamb waves.

Existing stress evaluation methods based on the Lamb waves mainly use the time of flight (TOF) or velocity as the means of stress measurement. However, these two features used for stress measurement are sometimes insensitive to stress changes. Therefore, it is essential to explore other features that are potentially more sensitive to stress changes. The time-frequency spectrums of signals containing stress information have not yet been fully studied for stress evaluation. This paper proposes a uniaxial stress measurement method based on two time-frequency characteristics of Lamb waves, i.e., the slope of time-frequency spectrum distribution (TFSD) and pulse width impact factor. Theoretical expressions of the slope of TFSD are derived. The impacts of excitation signal parameters (i.e., bandwidth and center frequency) and noise on two time-frequency characteristics were discussed. Then, the fitting results of the finite element simulation are consistent with the results predicted by theory. To experimentally validate the proposed theory, aluminum plate specimens with two different types of adhesives were used for the experiment. According to the experimental stress measurement expression, three uniaxial tensile tests in the range of 35-95 MPa were conducted on the identical batch of specimens. The maximum standard deviation of multiple measured stress based on pulse width impact factor is 3.76433 MPa, demonstrating excellent measurement stability. The maximum standard deviation of multiple measured stress based on the slope of TFSD is 9.12492 MPa. It shows that the proposed methodology is a promising alternative for stress measurement.

Higher cardiovascular disease risks in people living with HIV: A systematic review and meta-analysis.

Background: The prognosis of AIDS after active antiretroviral therapy (ART) and the quality of life of people living with HIV (PLWH) are both affected by non-AIDS-related diseases such as cardiovascular disease (CVD). However, the specific risk ratios between PLWH and individuals negative for HIV are poorly understood. We aimed to systematically review and investigate the CVD risk factors associated with HIV. Methods: We searched PubMed, Embase, Web of Science, and Cochrane Library databases between 1 January 2015, and 12 May 2023 for articles reported the prevalence and risk factors of CVD such as hypertension, dyslipidaemia, coronary artery disease (CAD), and myocardial infarction (MI). Due to the high heterogeneity, we used a random-effects model to analyse the data. All statistical analyses were performed using Stata/MP 17.0 with 95% confidence intervals (CIs). Results: We analysed 31 eligible studies including 312 913 PLWH. People living with HIV had higher risks of dyslipidaemia (hazard ratio (HR) = 1.53; 95% CI = 1.29, 1.82), CAD (HR = 1.37; 95% CI = 1.24, 1.51), and MI (HR = 1.47; 95% CI = 1.28, 1.68) compared to individuals without HIV. However, there were no significant differences in the prevalence of hypertension between groups (HR = 1.17; 95% CI = 0.97, 1.41). Subgroup analysis revealed that men with HIV, PLWH who smoked and the elderly PLWH had a high prevalence of CVD. Moreover, the disease prevalence patterns varied among regions. In the USA and Europe, for instance, some HRs for CVD were higher than in other regions. Active ART initiation after 2015 appears to have a lower risk of CVD (hypertension, hyperlipidaemia, CAD). All outcomes under analysis showed significant heterogeneity (I2>70%, P < 0.001), which the available study-level variables could only partially account for. Conclusions: People living with HIV had a higher CVD risk than the general population; thus, CVD prevention in PLWH requires further attention. Rapid initiation of ART may reduce the incidence of CVD in PLWH. For timely screening of CVD high-risk individuals and thorough disease management to prevent CVD, further studies are required to evaluate the risk factors for CVD among PLWH, such as age, region, etc. Registration: PROSPERO (CRD42021255508).

Efficacy and safety of a music-therapy facilitated pulmonary telerehabilitation program in COPD patients: the COPDMELODY study protocol.

Despite considerable evidence for the benefit in chronic obstructive pulmonary disease (COPD), the implementation of pulmonary rehabilitation (PR) is insufficient. However, music therapy may help address this gap due to its unique benefits. Therefore, we aimed to develop a music-therapy facilitated pulmonary telerehabilitation program based on rhythm-guided walking, singing, and objective telemonitoring. A supervised, parallel-group, single-blinded, randomized controlled clinical trial will be conducted, including 75 patients with COPD anticipated to be randomized in a 1:1:1 ratio into three groups. The intervention groups will receive a 12-week remotely monitored rehabilitation program, while the usual care group will not receive any rehabilitation interventions. Of the two intervention groups, the multi-module music therapy group will contain rhythm-guided walking and singing training, while the rhythm-guided walking group will only include music tempo-guided walking. The primary outcome is the distance of the incremental shuttle walking test. Secondary outcomes include respiratory muscle function, spirometry, lower extremity function, symptoms, quality of life, anxiety and depression levels, physical activity level, training adherence, and safety measurements. The results of this study can contribute to develop and evaluate a home-based music-facilitated rehabilitation program, which has the potential to act as a supplement and/or substitute (according to the needs) for traditional center-based PR in patients with stable COPD. Clinical trial registration: https://classic.clinicaltrials.gov/, NCT05832814.

Pulmonary rehabilitation restores limb muscle mitochondria and improves the intramuscular metabolic profile.

BACKGROUND: Exercise, as the cornerstone of pulmonary rehabilitation, is recommended to chronic obstructive pulmonary disease (COPD) patients. The underlying molecular basis and metabolic process were not fully elucidated. METHODS: Sprague-Dawley rats were classified into five groups: non-COPD/rest ( n  = 8), non-COPD/exercise ( n  = 7), COPD/rest ( n  = 7), COPD/medium exercise ( n  = 10), and COPD/intensive exercise ( n  = 10). COPD animals were exposed to cigarette smoke and lipopolysaccharide instillation for 90 days, while the non-COPD control animals were exposed to room air. Non-COPD/exercise and COPD/medium exercise animals were trained on a treadmill at a decline of 5° and a speed of 15 m/min while animals in the COPD/intensive exercise group were trained at a decline of 5° and a speed of 18 m/min. After eight weeks of exercise/rest, we used ultrasonography, immunohistochemistry, transmission electron microscopy, oxidative capacity of mitochondria, airflow-assisted desorption electrospray ionization-mass spectrometry imaging (AFADESI-MSI), and transcriptomics analyses to assess rectal femoris (RF). RESULTS: At the end of 90 days, COPD rats' weight gain was smaller than control by 59.48 ±â€Š15.33 g ( P  = 0.0005). The oxidative muscle fibers proportion was lower ( P  < 0.0001). At the end of additional eight weeks of exercise/rest, compared to COPD/rest, COPD/medium exercise group showed advantages in weight gain, femoral artery peak flow velocity (Δ58.22 mm/s, 95% CI: 13.85-102.60 mm/s, P  = 0.0104), RF diameters (Δ0.16 mm, 95% CI: 0.04-0.28 mm, P  = 0.0093), myofibrils diameter (Δ0.06 µm, 95% CI: 0.02-0.10 µm, P  = 0.006), oxidative muscle fiber percentage (Δ4.84%, 95% CI: 0.15-9.53%, P  = 0.0434), mitochondria oxidative phosphorylate capacity ( P  < 0.0001). Biomolecules spatial distribution in situ and bioinformatic analyses of transcriptomics suggested COPD-related alteration in metabolites and gene expression, which can be impacted by exercise. CONCLUSION: COPD rat model had multi-level structure and function impairment, which can be mitigated by exercise.

Prediction of exercise-induced desaturation in COPD patients without resting hypoxemia: a retrospective study.

BACKGROUND: There is no universally accepted criterion for assessing exercise-induced desaturation (EID). The purpose of this study is to compare the two methods regularly used for determining EID in COPD patients, as well as to explore the risk factors and predictors related to EID. METHODS: The 6MWT was performed with continuous SpO2 monitoring on patients with stable COPD. Using two methods (method A: "SpO2rest-SpO2min ≥ 4% and/or SpO2min < 90%", method B: "SpO2rest-SpO2end ≥ 4% and/or SpO2end < 90%") as EID determination criteria to assess the incidence of EID. The differences and consistency of the two methods are compared. Moreover, we collected data through the pulmonary function test, mMRC dyspnea score, COPD assessment test, BODE index and CT-defined emphysema. Univariate and multivariate logistic regression analyses were used to identify factors affecting the EID. For the parameters that predict EID in 6MWT, a receiver operating characteristic (ROC) curve analysis was employed. RESULTS: The analysis included 124 patients. The overall incidence of EID was 62.1% by using method A as the criterion and 51.6% by method B. All of the EID patients found by method B were included in the EID patients identified by method A, as well as 13 new-EID patients. The difference in diagnostic outcomes between the two approaches was not statistically significant (P > 0.05), but they were in excellent agreement (Kappa = 0.807, P = 0.001). Logistic regression analyses found that DLCO SB% pred, DLCO/VA% pred, CAT score, mean density, PD15, emphysema volume and %LAA were significant determinants of the EID. For predicting EID, the ROC analysis produced AUC and cutoffs of 0.689 and 50.45% (DLCO SB% pred), 0.707 and 75.0% (DLCO/VA% pred), 0.727 and 15 points (CAT score), 0.691 and - 955.00HU (PD15), 0.671 and - 856.46HU (mean density), 0.668 and 338.14 ml (emphysema volume) and 0.656 and 7.63% (%LAA), respectively. CONCLUSIONS: Two methods evaluating EID in this research are in a good agreement, method A can find more EID patients by focusing on SpO2min. When conditions are constrained, it is also sufficient to assess EID in COPD patients by method B. In terms of the predictors of EID, DLCO SB% pred, DLCO/VA% pred, CAT score and CT-defined emphysema are all statistically significant test variables to determine EID.

Ultrasonic array imaging of highly attenuative materials with spatio-temporal singular value decomposition.

With the increasing use of high density polyethylene (HDPE) pipes in nuclear industry which puts safety at the forefront, ultrasonic array imaging methods play a vital role in the structural integrity of HDPE pipe materials. However, the viscoelastic attenuation of HDPE pipe materials significantly decreases the level of signals, leading to a low signal-to-noise ratio caused by electronic noise. In this work, a domain-adapted spatio-temporal singular value decomposition (STSVD) processing algorithm combined with the total focusing method is proposed to improve the ultrasonic array image quality. First, the real-valued radio frequency (RF) data or A-scan signals are demodulated into the complex analytic signals containing in-phase and quadrature (I/Q) components. Then, the STSVD processing algorithm is used to filter the I/Q data, and the filtered I/Q data is converted into RF signals. Finally, the total focusing method is applied to the processed RF signals to produce the image of the region under detection as a stage of post-processing. Experiments are carried out with an ultrasonic linear phased array in contact with the HDPE pipe materials containing multiple side-drilled holes and through-wall notches. Results show that the proposed method can produce images with high quality to provide good inspection and characterization of defects in highly attenuative materials, especially the deeper defects.

High-copy genome integration and stable production of p-coumaric acid via a POT1-mediated strategy in Saccharomyces cerevisiae.

AIMS: To overcome the defective unstable production of p-coumaric acid (p-CA) using episomal plasmids and simultaneously achieve genetic stability and high-copy integration in Saccharomyces cerevisiae. METHODS AND RESULTS: Two-micron plasmids were used to obtain high titres of p-CA, but p-CA production was decreased significantly in a nonselective medium after 72 h. To overcome the defect of unstable p-CA production during fermentation, delta integration with the triosephosphate isomerase gene from Schizosaccharomyces pombe (POT1) was employed as a selection marker to integrate heterologous p-CA synthesis cassette, and the high-level p-CA-producing strain QT3-20 was identified. In shake flask fermentation, the final p-CA titre of QT3-20 reached 228.37 mg L-1 at 168 h, 11-fold higher than integrated strain QU3-20 using URA3 as the selective marker, and 9-fold higher than the best-performing episomal expression strain NKE1. Additionally, the p-CA titre and gene copy number remained stable after 100 generations of QT3-20 in a nonselective medium. CONCLUSION: We achieved high-copy genome integration and stable heterologous production of p-CA via a POT1-mediated strategy in S. cerevisiae. SIGNIFICANCE AND IMPACT OF STUDY: With superior genetic stability and production stability in a nonselective medium during fermentation, the high-level p-CA-producing strain constructed via POT1-mediated delta integration could serve as an efficient platform strain, to eliminate the threat of unstable and insufficient supply for future production of p-CA derivatives, make downstream processing and biosynthesis much simpler.

Developing Multi-Copy Chromosomal Integration Strategies for Heterologous Biosynthesis of Caffeic Acid in Saccharomyces cerevisiae.

Caffeic acid, a plant-sourced phenolic compound, has a variety of biological activities, such as antioxidant and antimicrobial properties. The caffeic acid biosynthetic pathway was initially constructed in S. cerevisiae, using codon-optimized TAL (coTAL, encoding tyrosine ammonia lyase) from Rhodobacter capsulatus, coC3H (encoding p-coumaric acid 3-hydroxylase) and coCPR1 (encoding cytochrome P450 reductase 1) from Arabidopsis thaliana in 2 µ multi-copy plasmids to produce caffeic acid from glucose. Then, integrated expression of coTAL via delta integration with the POT1 gene (encoding triose phosphate isomerase) as selection marker and episomal expression of coC3H, coCPR1 using the episomal plasmid pLC-c3 were combined, and caffeic acid production was proved to be improved. Next, the delta and rDNA multi-copy integration methods were applied to integrate the genes coC3H and coCPR1 into the chromosome of high p-coumaric acid yielding strain QT3-20. The strain D9 constructed via delta integration outperformed the other strains, leading to 50-fold increased caffeic acid production in optimized rich media compared with the initial construct. The intercomparison between three alternative multi-copy strategies for de novo synthesis of caffeic acid in S. cerevisiae suggested that delta-integration was effective in improving caffeic acid productivity, providing a promising strategy for the production of valuable bio-based chemicals in recombinant S. cerevisiae.

Improving the Level of the Tyrosine Biosynthesis Pathway in Saccharomyces cerevisiae through HTZ1 Knockout and Atmospheric and Room Temperature Plasma (ARTP) Mutagenesis.

In recent years, many studies have been conducted on the expression of multiple aromatic compounds by Saccharomyces cerevisiae. The concentration of l-tyrosine, as a precursor of such valuable compounds, is crucial for the biosynthesis of aromatic metabolites. In this study, a novel function of HTZ1 was found to be related to tyrosine biosynthesis, which has not yet been reported. Knockout of this gene could significantly improve the ability of yeast cells to synthesize tyrosine, and its p-coumaric acid (p-CA) titer was approximately 3.9-fold higher than that of the wild-type strain BY4742. Subsequently, this strain was selected for random mutagenesis through an emerging mutagenesis technique, namely, atmospheric and room temperature plasma (ARTP). After two rounds of mutagenesis, five tyrosine high-producing mutants were obtained. The highest production of p-CA was 7.6-fold higher than that of the wild-type strain. Finally, transcriptome data of the htz1Δ strain and the five mutants were analyzed. The genome of mutagenic strains was also resequenced to reveal the mechanism underlying the high titer of tyrosine. This system of target engineering combined with random mutagenesis to screen excellent mutants provides a new basis for synthetic biology.

Multi-mode reverse time migration damage imaging using ultrasonic guided waves.

The sensitivity of Lamb wave modes to a particular defect or instance of damage is dependent on various factors (e.g., the local strain energy density due to that wave mode). As a result, different modes will be more useful than others for damage detection and quantification, dependent on damage type and location. For example, prior work in the field has shown that out-of-plane modes may have a higher sensitivity than in-plane modes to surface defects in plates. The excitability of a certain data acquisition system and the corresponding resolution for damage imaging also varies with frequency. The aim of the present work was to develop a multi-mode damage imaging technique that enables characterization of damage type and size, general sensitivity to unknown damage types, higher resolution imaging, and detectability regardless of the data acquisition system used. A reverse-time migration (RTM) imaging algorithm was combined with a numerical simulator-the three-dimensional (3D) elastodynamic finite integration technique (EFIT)-to provide multi-mode damage imaging. The approach was applied to two simulated case studies featuring damaged isotropic plates. Sensitivities of damage type to wave mode were investigated by separating the A0 and S0 Lamb wave modes obtained from the resultant RTM wavefields.