BACKGROUND: Mesenchymal stromal cell (MSC) therapy holds great potential yet efficacy and safety concerns with cell therapy persist. The beneficial effects of MSCs are often attributed to their secretome that includes extracellular vesicles (EVs). EVs carry biologically active molecules, protected by a lipid bilayer. However, several barriers hinder large-scale MSC EV production. A serum-free culturing approach is preferred for producing clinical-grade MSC-derived EVs but this can affect both yield and purity. Consequently, new strategies have been explored, including genetically engineering MSCs to alter EV compositions to enhance potency, increase circulation time or mediate targeting. However, efficient transfection of MSCs is challenging. Typical sources of MSC include adipose tissue and bone marrow, which both require invasive extraction procedures. Here, we investigate the use of urine-derived stem cells (USCs) as a non-invasive and inexhaustible source of MSCs for EV production.
METHODS: We isolated, expanded, and characterized urine-derived stem cells (USCs) harvested from eight healthy donors at three different time points during the day. We evaluated the number of clones per urination, proliferation capacity and conducted flow cytometry to establish expression of surface markers. EVs were produced in chemically defined media and characterized. PEI/DNA transfection was used to genetically engineer USCs using transposon technology.
RESULTS: There were no differences between time points for clone number, doubling time or viability. USCs showed immunophenotypic characteristics of MSCs, such as expression of CD73, CD90 and CD105, with no difference at the assessed time points, however, male donors had reduced CD73 + cells. Expanded USCs were incubated without growth factors or serum for 72 h without a loss in viability and EVs were isolated. USCs were transfected with high efficiency and after 10 days of selection, pure engineered cell cultures were established.
CONCLUSIONS: Isolation and expansion of MSCs from urine is non-invasive, robust, and without apparent sex-related differences. The sampling time point did not affect any measured markers or USC isolation potential. USCs offer an attractive production platform for EVs, both native and engineered.

OBJECTIVE: This study aimed to analyze the predictive value of caudate to right lobe ratio (CRL-R) and liver segmental volume ratio (LSVR) for chronic liver disease (CLD) on routine abdominal CT scans and their association with 5-year decompensation- and transplant-free survival.
METHODS: This retrospective study included 108 patients without CLD and 98 patients with biopsy-proven CLD. All patients underwent abdominal CT scans between 03/2015 and 08/2017. Patients with CLD were divided into three groups: early CLD (F0-F2; eCLD; n = 40), advanced CLD (F3-F4; aCLD; n = 20), and aCLD with clinically significant portal hypertension (aCLDPH; n = 38). CRL-R and LSVR were compared between groups using Kruskal-Wallis test and ROC analysis to determine cutoff-values. 5-year decompensation- and transplant-free survival were assessed by Kaplan-Meier curve analysis.
RESULTS: CRL-R and LSVR were significantly different between all groups (p < 0.001). A CRL-R cutoff-value of > 0.99 predicted aCLD with a sensitivity of 69% and a specificity of 80% (AUC = 0.75, p < 0.001), while LSVR > 0.37 had a sensitivity of 67% and a specificity of 84% (AUC = 0.80, p < 0.001). CLD-patients with both CRL-R > 0.99 and LSVR > 0.37 had a significantly lower probability of 5-year decompensation-free survival (31%) as well as lower probability of 5-year transplant-free survival (41%) than those with a CRL-R < 0.99 and/or LSVR < 0.37 (70%, 62%, p = 0.006, p = 0.038).
CONCLUSIONS: CRL-R and LSVR showed a high predictive value for CLD on routine abdominal CT scans. In patients with CLD, both CRL-R and LSVR may be combined and are associated with 5-year decompensation-free and transplant-free survival.

OBJECTIVE: To compare multiple noninvasive ECG methods in pond sliders based upon repeatability, ability to recognize standard waveforms, and measurability.
METHODS: The study was performed from November 2023 through January 2024. Ten healthy adult pond turtles were enrolled in the study. ECG tracings were obtained using 4 previously reported and 1 novel ECG methodology, using adhesive patches applied to the prehumeral fossae and abdominal scutes. The 50 ECG tracings were blinded by method and turtle, randomized for evaluation by 4 observers, and assessed for quality on a scale from 0 to 3.
RESULTS: Interobserver and intraobserver intraclass correlation coefficients for all tracings were 0.84 and 0.97, respectively, indicating an almost perfect agreement. The average score amongst the observers for each tracing was then averaged by method, ranging from 0.875 to 2.15. The novel method demonstrated a collective average of 2.15 and was the highest scoring method for 8 of 10 turtles.
CONCLUSIONS: Electrocardiogram utilizing methods that apply adhesive patches to the prehumeral fossae and either the abdominal scutes of the plastron or prefemoral fossae in pond turtles can be performed to produce recognizable waveforms.
CONCLUSIONS: Diagnostic tools, such as ECGs, are imperative to enhance veterinary care in nonconventional species, particularly with the rising trend of exotic pets worldwide.

Adjusting the catalytic activity of nanozymes for enhanced oncotherapy has attracted significant interest. However, it remains challenging to engineer regulatory tactics with a minimal impact on normal tissues. By exploiting the advantages of energy storage, photostimulated, and long afterglow luminescence of persistent nanoparticles (PLNPs), a persistent luminescence-based nanoreservoir was produced to improve its catalytic activity for benign oncotherapy. In the study, PLNPs in a nanoreservoir with the ability to store photons served as a self-illuminant to promote its peroxidase-like activity and therapeutic efficacy by persistently motivating its photothermal effect before and after external irradiation ceased. The photostimulated and persistent luminescence of PLNPs and spatiotemporal controllability of exogenous light jointly alleviated adverse effects induced by prolonged irradiation and elevated the catalytic capability of the nanoreservoir. Ultimately, the system fulfilled benign photothermal-intensive nanozymatic therapy. This work provides new insights into boosting the catalytic activity of nanozymes for secure disease treatment.

Low back pain (LBP) is the leading cause of disability worldwide, yet its quantitative and noninvasive assessment remains challenging. Considering that near-infrared spectroscopy (NIRS) became a promising noninvasive tool for monitoring muscle and cupping therapy could regulate muscle blood flow to relieve LBP, we attempted to incorporate cupping and hemodynamics monitoring in muscle tissue by NIRS to assess LBP. We collected 3-min NIRS recordings on 12 LBP patients and 12 healthy subjects before and after 20-min cupping. Initially, no significant hemodynamic differences were observed between the groups. After cupping, the concentration changes of oxy-hemoglobin (Δ[HbO2]) in the emitter-detector channel parallel to spine unexpectedly exhibited that LBP was remarkably lower by approximately 67% compared with the controls. This study highlighted the potential of combining NIRS and cupping protocol as a quantitative assessment technique for LBP, also providing a new idea for clinical integration of novel optical assessment technologies.

BACKGROUND: Ventricular tachycardia is an irregular heartbeat conventionally treated using invasive cardiac catheter ablation and medication. However, when standard treatments have been exhausted, cardiac SABR provides a final treatment option to this high-mortality condition. Complex diagnostic mapping and planning scans enable multi-disciplinary target delineation for a 25Gy single fraction. However, organs at risk (OAR) near the target make this treatment challenging to plan and deliver. Publications from cardiologists report the efficacy of cardiac SABR, however there is limited data on the treatment delivery and image matching of this complex procedure.
METHODS: Four specialist therapeutic radiographers experienced in cardiac SABR reviewed 40 CBCTs from 10 patients treated in the UK. Each therapeutic radiographer conducted five image matches: a manual match (manual), an automatic match to the heart structure (auto) and the auto match followed by manual adjustment to the PTV (PTV), all using three degrees of freedom (DoF) only. The auto and PTV matches were also repeated using 6DoF. Inter-observer variability was quantified using 95% limits of agreement from a modified Bland-Altman analysis.
RESULTS: The limits of agreement were smallest in the automatic matches suggesting the algorithm is reliable. A manual adjustment from the auto match to the PTV is clinically appropriate to optimise target coverage. The limits of agreement were smaller in the 6DoF PTV match 1.06 mm, 1.24 mm, 1.68 mm than the 3DoF PTV match 1.57 mm, 2.06 mm, 2.11 mm (lateral, vertical, longitudinal).
CONCLUSIONS: The 6DoF CBCT image match has less variability and therefore suggest using a 6DoF couch for treatment delivery.
CONCLUSIONS: Cardiac SABR CBCT image matching at treatment delivery is complex, optimisation of CBCT acquisition parameters and therapeutic radiographer training is essential prior to implementation.

OBJECTIVE: To gather information on practices and perceptions of high-performance experts regarding their athletes\' muscle fiber-type composition (MFTC) and its estimation.
METHODS: A questionnaire on the noninvasive versus invasive estimation of MFTC was completed by 446 experts including coaches and sport-science/sports-medicine staff. Moreover, the perceived importance of MFTC for training and performance optimization was assessed. Differences between sport types (individual and team sports) were analyzed using chi-square tests.
RESULTS: Forty percent of the experts implemented MFTC assessment in pursuit of performance optimization, while 50% did not know their athletes\' MFTC but expressed a desire to implement it if they would be able to assess MFTC. Ten percent did not perceive value in MFTC assessment. Only 18% of experts believed that their athletes would undergo a muscle biopsy, leading to the adoption of alternative noninvasive techniques. Experts primarily relied on their experience to estimate MFTC (65%), with experts working in individual sports using their experience more frequently than those working in team sports (68% vs 51%; P = .009). Jump tests emerged as the second-most commonly employed method for estimating MFTC (56%). When only considering experts who are currently using MFTC, 87% use MFTC to individualize training volume and 84% to individualize training intensity.
CONCLUSIONS: Experts value MFTC assessment primarily to individualize training but mainly rely on noninvasive methods to estimate MFTC. Some of these methods lack scientific validity, suggesting a continuing need for education and further research in this area.

Pharmaceutical research is increasingly focusing on transdermal drug delivery due to its potential for improved compliance and bioavailability. However, it is challenging due to the tight intracellular junctions present in the skin. Researchers have developed noninvasive methods, like transfersomes, to overcome these challenges. Transfersomes are ultra-deformable vesicles utilized for improved transdermal applications. They are made up of a phospholipid-rich lipid bilayer, an edge activator, and an ethanol/aqueous core. After topical treatment, transfersomes can penetrate deeper skin regions, delivering larger concentrations of active compounds. A transfersomal patch is applied to the skin and left for an extended period of time to allow a large dose of medication to permeate into the bloodstream. The transfersomal patch offers an advantage over the transfersomal gel because it allows the transfersomes to be applied under occlusive conditions, resulting in greater permeability, a lower amount of active medication, and a steady supply rather than a massive dose. This review represents the preparation and evaluation of transfersomal patches, recent research approaches, and future aspects of transfersomal patches. This study suggests that drug-loaded transfersomal patches could be a unique option to avoid invasive therapy.

OBJECTIVE: Transcranial ultrasound neuromodulation (TUSN) is a noninvasive and spatially specific therapy that promises to deliver treatments tailored to the specific needs of individuals. To fulfill this promise, each treatment must be modified to adequately correct for variation across individual skulls and neural anatomy. This study examines the use of ultrasound-induced voltage potentials (measured with electroencephalography [EEG]) to guide TUSN therapies.
METHODS: We measured EEG responses in two awake nonhuman primates during sonication of 12 targets surrounding two deep brain nuclei, the left and right lateral geniculate nucleus.
RESULTS: We report reliable ultrasound evoked potentials measured with EEG after the deep brain ultrasonic modulation in nonhuman primates. Robust responses are observed after just ten repetitions of the ultrasonic stimuli. Moreover, these potentials are only evoked for specific deep brain targets. Furthermore, a behavioral study in one subject shows a direct correspondence between the target with maximal EEG response and ultrasound-based modulation of visual choice behavior. Thus, this study provides evidence for the feasibility of EEG-based guidance for ultrasound neuromodulation therapies.

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