Macrophages in the Context of Muscle Regeneration and Duchenne Muscular Dystrophy.

Macrophages are essential to muscle regeneration, as they regulate inflammation, carry out phagocytosis, and facilitate tissue repair. These cells exhibit phenotypic switching from pro-inflammatory (M1) to anti-inflammatory (M2) states during muscle repair, influencing myoblast proliferation, differentiation, and myofiber formation. In Duchenne Muscular Dystrophy (DMD), asynchronous muscle injuries disrupt the normal temporal stages of regeneration, leading to fibrosis and failed regeneration. Altered macrophage activity is associated with DMD progression and physiopathology. Gaining insight into the intricate relationship between macrophages and muscle cells is crucial for creating effective therapies aimed at treating this muscle disorder. This review explores the dynamic functions of macrophages in muscle regeneration and their implications in DMD.

Endothelial NO synthase 786T/T polymorphism increases hemorrhagic transformation after endovascular thrombectomy.

BACKGROUND AND PURPOSE: This study examined whether the 786 NOS3 polymorphism is associated with the risk of hemorrhagic transformation (HT) in stroke patients with anterior large vessel occlusion (ALVO) treated using endovascular thrombectomy (EVT). METHODS: We performed an observational cohort study that included 118 patients with ALVO who underwent EVT. HT was assessed in follow-up CT and MRI. HT and non-HT patients were compared in terms of the 786 NOS3 polymorphism, flow mediated dilation (FMD) values within 3 days after the stroke, and collateral status based on three grading scales. Demographics, vascular risk factors, additional radiological data including ASPECT score, thrombus length and infarct size, and EVT procedure and outcome variables were also included. RESULTS: Radiological HT occurred in 55 (46.6%) patients and the 786T/T NOS3 polymorphism was associated with HT (unadjusted OR of 2.33, 95%CI: 1.05-5.20, adjusted OR of 3.14, 95%CI: 1.16-8.54). Collateral status and systemic endothelial function assessed by FMD were not mediators of this relationship as no differences were seen in the median FMD percentage values or collateral status between NOS3 genotypes. CONCLUSIONS: Our results suggest that genetic variations affecting the NO pathway, such as the 786 NOS3 polymorphism, may contribute to individual variability in the occurrence of HT and these results support involvement of this pathway in the pathogenesis of ischemia-reperfusion injury after EVT.

Improving river hydromorphological assessment through better integration of riparian vegetation: Scientific evidence and guidelines.

River hydromorphology has long been subjected to huge anthropogenic pressures with severe negative impacts on related ecosystems' functioning and water quality. Therefore, improving river hydromorphological conditions represents a priority task in sustainable river management and requires proper assessment tools. It is well known that riparian vegetation plays a crucial role in sustaining river hydromorphological conditions. However, it has been nearly neglected in most hydromorphological assessment protocols, including the European Water Framework Directive (WFD). This paper reviews and synthesizes the relevance of riparian vegetation for river hydromorphology, focusing on its contribution to streamflow and sediment regime conditions. We also examine how riparian vegetation is considered in the WFD and how it is included in national hydromorphological protocols currently in use. Our findings point to a temporal mismatch between the date when the WFD came into force and the emergence of scientific and technologic advances in riparian vegetation dynamism and bio-geomorphic modeling. To overcome this misalignment, we present promising approaches for the characterization and assessment of riparian vegetation, which include the identification of vegetation units and indicators at multiple scales to support management and restoration measures. We discuss the complexity of riparian vegetation assessment, particularly with respect to the establishment of river-type-based reference conditions and the monitoring and management targets, and propose some attributes that can serve as novel indicators of the naturalness vs. artificiality of riparian vegetation. We argue that the hydromorphological context of the WFD should be revisited and offer guidance to integrate riparian vegetation in river hydromorphological monitoring and assessment.

Pelvic floor and abdominal muscle responses during hypopressive exercises in women with pelvic floor dysfunction.

AIM: To measure the neuromuscular activation of the pelvic floor and abdominal muscles concurrently with vaginal closure forces induced during a hypopressive exercise (HE) and to identify the contribution of the HEs sequences (posture and maneuver) in the muscle's activation. METHODS: A cross-sectional study design was employed. Sixty-six women who had participated in a physical therapy program focused on HEs were recruited. Pelvic floor muscle (PFM) activation was measured using surface electromyography (sEMG) in supine and in the orthostatic position, and vaginal closure force was measured through vaginal dynamometry in supine. Activation of the abdominal, gluteal, and hip adductor muscles was measured using sEMG. Maximum effort voluntary contractions (MVCs) of the PFMs and reference contractions of the abdominal and hip muscles were acquired for normalization purposes. A HE was then performed in a supine position with one leg raised, then in an orthostatic position. RESULTS: During the supine HE, the peak PFM sEMG amplitude was 74.4% to 86.5% (49.6%-109.6%) of MVC, the peak vaginal closure force was between 51.2% and 55.7% (95.5%-382.9%) of MVC, and the muscles of the lateral abdominal wall were activated between 25.4% and 35.3% of the reference contraction. During the orthostatic HE, PFM activation was 61.4% (40.1%-105.6%) of MVC, and the lateral abdominal wall muscles contracted at 22.8% of the reference activation level. CONCLUSIONS: The PFMs, abdominal, gluteal, and adductor muscles are activated during the performance of a HE. The activation level of the PFMs and abdominal muscles is likely insufficient to result in strength gains; however, they could have an endurance effect.

Effectiveness of four types of bandages and kinesio-tape for treating breast-cancer-related lymphoedema: a randomized, single-blind, clinical trial.

OBJECTIVE: To compare the effects of four types of bandages and kinesio-tape and determine which one is the most effective in women with unilateral breast cancer-related lymphoedema. DESIGN: Randomized, single-blind, clinical trial. SETTING: Physiotherapy department in the Women's Health Research Group at the University of Alcalá, Madrid, Spain. SUBJECTS: A total of 150 women presenting breast-cancer-related lymphoedema. INTERVENTIONS: Participants were randomized into five groups (n = 30). All women received an intensive phase of complex decongestive physiotherapy including manual lymphatic drainage, pneumatic compression therapy, therapeutic education, active therapeutic exercise and bandaging. The only difference between the groups was the bandage or tape applied (multilayer; simplified multilayer; cohesive; adhesive; kinesio-tape). MAIN MEASUREMENTS: The main outcome was percentage excess volume change. Other outcomes measured were heaviness and tightness symptoms, and bandage or tape perceived comfort. Data were collected at baseline and finishing interventions. RESULTS: This study showed significant differences between the bandage groups in absolute value of excess volume (P < 0.001). The most effective were the simplified multilayer (59.5%, IQR = 28.7) and the cohesive bandages (46.3%, IQR = 39). The bandages/tape with the least difference were kinesio-tape (4.9%, IQR = 17.7) and adhesive bandage (21.7%, IQR = 17.9). The five groups exhibited a significant decrease in symptoms after interventions, with no differences between groups. In addition, kinesio-tape was perceived as the most comfortable by women and multilayer as the most uncomfortable (P < 0.001). CONCLUSION: Simplified multilayer seems more effective and more comfortable than multilayer bandage. Cohesive bandage seems as effective as simplified multilayer and multilayer bandage. Kinesio taping seems the least effective.

A new ranking scale for assessing leaching potential pollution from abandoned mining wastes based on the Mexican official leaching test.

Potentially toxic elements (PTEs) present in abandoned mining wastes (AMW) are of great concern because of potential risks to human health and ecosystems. Indices of contamination (IC) applied to mining wastes are calculated using the total concentration of PTEs and comparing them with regional geochemical backgrounds. However, determining the total content of heavy metals is insufficient to assess the hazard of mining wastes. Therefore, in addition to total concentration, the potential risk is also evaluated through water mobility of elements. Accordingly, leaching procedures are useful tools for the geochemical characterization of soluble constituents that are mobilized. In this study, the solubility of PTEs from different types of mining wastes is comparatively assessed using three standard leaching methods (European; U.S. Geological Survey and; Mexican). The Hazard Average Quotient (HAQ) was calculated to assess the potential Toxicity Factor (TF). TF is an indicator of the relative potential toxicity of wastes and is the basis for the classification of AMW. A comparative assessment provides evidence that there are no statistically significant differences in PTEs solubility by the three leaching methods and it was also found that the pH of the eluates was dictated by the type of waste. Results suggest that the IC gives an indicator of the potential contamination of soils and sediments by erosive processes, or a long-term measure, whereas TF assesses the possibility of contaminating water in the short term. The most significant finding is the new ranking scale of TF, as a function of HAQ, applied to the Mexican standard leaching test. This factor, together with other considerations relating to risk-generating processes, might then be applied in places having large amounts of recorded AMW, such as the Iberian Peninsula and Latin America, where effective management is required to rank sites, based on preliminary environmental and human risk assessment.

Geochemical anomalies for the determination of surface stream sediments pollution: case of Sierra de Cartagena-La Unión mining district, Spain.

This work explores the ability of the Spanish Geochemical Database to identify the existence of polluted stream sediments due to the presence of abandoned mine wastes. The mining district of Sierra de Cartagena-La Unión has been used as test area. A total of 18 abandoned tailings facilities were selected and samples were taken for analysis of the content in potential toxic elements. The results were contrasted with geochemical background values in order to identify which geochemical elements could entail anomalies potentially reflected in the Spanish Geochemical Database. For the study area, As, Cd, Pb, and Zn have been identified as potential toxic elements which can be used as geochemical indicators of sediment pollution processes originated in abandoned mine wastes. Furthermore, the correlation between Cd and Zn allows them to be considered as the best indicators of potential sediment contamination. The study of anomaly thresholds, through the analysis of accumulated frequencies of the contents of these elements in the sediments of the Spanish Geochemical Database, allows identifying sediments that may have been contaminated. A Mann-Whitney test contrasting the data of tailings, polluted sediments, and non-polluted sediments has been performed in order to verify differences among these types of samples. In addition, a geospatial analysis has demonstrated a very close relationship between contaminated sediments and the presence of mining wastes upstream. This methodology can be applied to any other mining region, to recognize the possible influence of pollution processes derived from the presence of abandoned mine wastes taking advantage of existing geochemical databases.

Allocation to Matched Related or Unrelated Donor Results in Similar Clinical Outcomes without Increased Risk of Failure to Proceed to Transplant among Patients with Acute Myeloid Leukemia: A Retrospective Analysis from the Time of Transplant Approval.

Clinical outcomes after allogeneic hematopoietic stem cell transplantation (allo-SCT) from unrelated donors (URDs) approach those of matched related donor (MRD) transplants in patients with acute myeloid leukemia (AML). Yet, available data fail to account for differences in pretransplantation outcomes between these donor selection strategies. In this regard, URD allo-HSCT is associated with longer waiting times to transplantation, potentially resulting in higher probabilities of failure to reach transplant. We retrospectively analyzed 108 AML patients accepted for first allo-HSCT from the time of approval to proceed to transplant. Fifty-eight (54%) patients were initially allocated to MRD, while URD search was initiated in 50 (46%) patients. Time to transplant was longer in patients allocated to a URD when compared with patients assigned to an MRD (median 142 days versus 100 days; p < .001). Forty-three of 58 (74%) patients in the MRD group and 35 of 50 (70%) patients in the URD group underwent transplantation (odds ratio [OR], 1.22; p = .63). Advanced disease status at the time of allo-HSCT approval was the only predictor of failure to reach transplantation in the multivariate analysis (OR, 4.78; p = .001). Disease progression was the most common cause of failure to reach allo-HSCT (66.7%) in both the MRD and URD groups. With a median follow-up from transplantation of 14.5 (interquartile range, 5 to 29) months, the 2-year estimate of overall survival (OS) from allo-HSCT was 46% in the MRD group and 57% in the URD group (p = .54). There were no differences in OS according to donor type allocation in the multivariate analysis (hazard ratio, 1.01; p = .83). When including patients from the time of transplant approval, 2-year OS was 39% in the MRD group versus 42% in the URD group. Our study suggests that allocation of AML patients to URDs may result in comparable clinical outcomes to MRD assignment without a significant increase in the risk of failure to reach transplant.

The evaluation of pelvic floor muscle strength in women with pelvic floor dysfunction: A reliability and correlation study.

AIMS: The purposes of this study were: (i) to evaluate the reliability of vaginal palpation, vaginal manometry, vaginal dynamometry; and surface (transperineal) electromyography (sEMG), when evaluating pelvic floor muscle (PFM) strength and/or activation; and (ii) to determine the associations among PFM strength measured using these assessments. METHODS: One hundred and fifty women with pelvic floor disorders participated on one occasion, and 20 women returned for the same investigations by two different raters on 3 different days. At each session, PFM strength was assessed using palpation (both the modified Oxford Grading Scale and the Levator ani testing), manometry, and dynamometry; and PFM activation was assessed using sEMG. RESULTS: The interrater reliability of manometry, dynamometry, and sEMG (both root-mean-square [RMS] and integral average) was high (Lin's Concordance Correlation Coefficient [CCC] = 0.95, 0.93, 0.91, 0.86, respectively), whereas the interrater reliability of both palpation grading scales was low (Cohen's Kappa [k] = 0.27-0.38). The intrarater reliability of manometry (CCC = 0.96), and dynamometry (CCC = 0.96) were high, whereas intrarater reliability of both palpation scales (k = 0.78 for both), and of sEMG (CCC = 0.79 vs 0.80 for RMS vs integral average) was moderate. The Bland-Altman plot showed good inter and intrarater agreement, with little random variability for all instruments. The correlations among palpation, manometry, and dynamometry were moderate (coefficient of determination [r2 ] ranged from 0.52 to 0.75), however, transperineal sEMG amplitude was only weakly correlated with all measures of strength (r2 = 0.23-0.30). CONCLUSIONS: Manometry and dynamometry are more reliable tools than vaginal palpation for the assessment of PFM strength in women with pelvic floor disorders, especially when different raters are involved. The different PFM strength measures used clinically are moderately correlated; whereas, PFM activation recorded using transperineal sEMG is only weakly correlated with PFM strength. Results from perineal sEMG should not be interpreted in the context of reporting PFM strength.

Regeneration of Salicaceae riparian forests in the Northern Hemisphere: A new framework and management tool.

Human activities on floodplains have severely disrupted the regeneration of foundation riparian shrub and tree species of the Salicaceae family (Populus and Salix spp.) throughout the Northern Hemisphere. Restoration ecologists initially tackled this problem from a terrestrial perspective that emphasized planting. More recently, floodplain restoration activities have embraced an aquatic perspective, inspired by the expanding practice of managing river flows to improve river health (environmental flows). However, riparian Salicaceae species occupy floodplain and riparian areas, which lie at the interface of both terrestrial and aquatic ecosystems along watercourses. Thus, their regeneration depends on a complex interaction of hydrologic and geomorphic processes that have shaped key life-cycle requirements for seedling establishment. Ultimately, restoration needs to integrate these concepts to succeed. However, while regeneration of Salicaceae is now reasonably well-understood, the literature reporting restoration actions on Salicaceae regeneration is sparse, and a specific theoretical framework is still missing. Here, we have reviewed 105 peer-reviewed published experiences in restoration of Salicaceae forests, including 91 projects in 10 world regions, to construct a decision tree to inform restoration planning through explicit links between the well-studied biophysical requirements of Salicaceae regeneration and 17 specific restoration actions, the most popular being planting (in 55% of the projects), land contouring (30%), removal of competing vegetation (30%), site selection (26%), and irrigation (24%). We also identified research gaps related to Salicaceae forest restoration and discuss alternative, innovative and feasible approaches that incorporate the human component.

Modeling Ti/Ge Distribution in LiTi2-xGex(PO4)3 NASICON Series by (31)P MAS NMR and First-Principles DFT Calculations.

Ti/Ge distribution in rhombohedral LiTi2-xGex(PO4)3 NASICON series has been analyzed by (31)P magic-angle spinning nuclear magnetic resonance (MAS NMR) spectroscopy and first-principles density functional theory (DFT) calculations. Nuclear magnetic resonance is an excellent probe to follow Ti/Ge disorder, as it is sensitive to the atomic scale environment without long-range periodicity requirements. In the samples considered here, PO4 units are surrounded by four Ti/Ge octahedra, and then, five different components ascribed to P(OTi)4, P(OTi)3(OGe), P(OTi)2(OGe)2, P(OTi)(OGe)3, and P(OGe)4 environments are expected in (31)P MAS NMR spectra of R3̅c NASICON samples. However, (31)P MAS NMR spectra of analyzed series display a higher number of signals, suggesting that, although the overall symmetry remains R3̅c, partial substitution causes a local decrement in symmetry. With the aid of first-principles DFT calculations, 10 detected (31)P NMR signals have been assigned to different Ti4-nGen arrangements in the R3 subgroup symmetry. In this assignment, the influence of octahedra of the same or different R2(PO4)3 structural units has been considered. The influence of bond distances, angles and atom charges on (31)P NMR chemical shieldings has been discussed. Simulation of the LiTi2-xGex(PO4)3 series suggests that detection of 10 P environments is mainly due to the existence of two oxygen types, O1 and O2, whose charges are differently affected by Ge and Ti occupation of octahedra. From the quantitative analysis of detected components, a random Ti/Ge distribution has been deduced in next nearest neighbor (NNN) sites that surround tetrahedral PO4 units. This random distribution was supported by XRD data displaying Vegard's law.

Water-Free Proton Conduction in Discotic Pyridylpyrazolate-based Pt(II) and Pd(II) Metallomesogens.

In this work we report on water-free proton conductivity in liquid-crystal pyridylpyrazolate-based Pt(II) and Pd(II) complexes [M(pz(R(n,n)py))2] (pz(R(n,n)py) = 3-(3,5-dialkyloxyphenyl)-5-(pyridin-2-yl)pyrazolate, R(n,n) = C6H3(OCnH2n+1)2; n = 4, 12, 16, M = Pd; n = 12, M = Pt) with potential application as electrolyte materials in proton exchange membrane fuel cells. The columnar ordering of the complexes in the liquid-crystalline phase opens nanochannels, which are used for fast proton exchange as detected by impedance spectroscopy and NMR. The NMR spectra indicate that the proton conduction mechanism is associated with a novel C-H···N proton transfer, which persists above the clearing point of the material. The highest conductivity of ∼0.5 µS cm(-1) at 180 °C with an activation energy of 1.2 eV is found for the Pt(II) compound in the mesophase. The Pd(II) complexes with different chain length (n = 4, 12, and 16) show lower conductivity but smaller activation energies, in the range of 0.74-0.93 eV.

Spanish cultural adaptation and validation of the shoulder pain and disability index, and the oxford shoulder score after breast cancer surgery.

BACKGROUND: The Oxford Shoulder Score (OSS) and the Shoulder Pain and Disability Index (SPADI) are patient-based outcome scores with valid psychometric properties which are widely used for shoulder interventions. OBJECTIVE: The purpose of the study is to adapt both questionnaires cross-culturally to Spanish, and to test their reliability, validity, responsiveness, and feasibility. DESIGN: Cultural adaptation and psychometric validation study. METHODS: Consecutive patients who had undergone breast cancer surgery referred to an outpatient clinic at the University of Alcalá de Henares, Spain. One hundred and twenty women who had undergone breast cancer surgery, with pain and shoulder dysfunction. Cross-cultural adaptation was performed according to the international guidelines. Reliability was analysed by test-retest reliability and internal consistency. Content and convergent construct validity were measured by the Expert Committee's and Spearman coefficient respectively. Responsiveness, feasibility, floor and ceiling effects were also tested. RESULTS: One hundred and twenty women aged 54.2 (±11) years took part in the study. The reliability was excellent; test-retest reliability was 0.974 (p < 0.001) for OSS, and 0.992 (p < 0.001) for SPADI; and Cronbach's alpha value was 0.947 for OSS, and 0.965 for SPADI. High construct validity was found between the OSS and SPADI questionnaires (r = -0.674). The effect size (ES) and standardized response mean (SRM) was moderate in OSS (ES = 0.50 and SRM = 0.70 (p < 0.001)), and moderate to good in SPADI (ES = 0.59 and SRM = 0.82 (p < 0.001)). LIMITATIONS: This study has some limitations, such as the group of participants is composed only of women following breast cancer treatment; the measurement took place in a single centre; and all the questionnaires administered were always provided to the participants in the same order. CONCLUSIONS: The OSS and SPADI Spanish versions are applicable, reliable, valid, and responsive to assess shoulder symptoms and quality of life in Spanish women with shoulder pain and disability after breast cancer treatment.

Comparison of dust release from epoxy and paint nanocomposites and conventional products during sanding and sawing.

The release of dust generated during sanding or sawing of nanocomposites was compared with conventional products without nanomaterials. Epoxy-based polymers with and without carbon nanotubes, and paints with different amounts of nano-sized titanium dioxide, were machined in a closed aerosol chamber. The temporal evolution of the aerosol concentration and size distribution were measured simultaneously. The morphology of collected dust by scanning electron microscopy was different depending on the type of nanocomposites: particles from carbon nanotubes (CNTs) nanocomposites had protrusions on their surfaces and aggregates and agglomerates are attached to the paint matrix in particles emitted from alkyd paints. We observed no significant differences in the particle size distributions when comparing sanding dust from nanofiller containing products with dust from conventional products. Neither did we observe release of free nanomaterials. Instead, the nanomaterials were enclosed or partly enclosed in the matrix. A source strength term Si (cm(-3) s(-1)) that describes particle emission rates from continuous sources was introduced. Comparison between the Si parameters derived from sanding different materials allows identification of potential effects of addition of engineered nanoparticles to a composite.

Combined Ultrahypofractionated Whole-Breast Irradiation and IORT-Boost: A Safety and Feasibility Analysis.

BACKGROUND: The current standard of local treatment for patients with localized breast cancer (BC) includes whole breast irradiation (WBI) after breast-conserving surgery (BCS). Ultrahypofractionated WBI schemes (1-week treatment) were shown not to be inferior to the standard WBI. Tumor bed boost using photon intraoperative radiotherapy (IORT) is safe and feasible in combination with standard WBI. The aim of the present study is to assess, for the first time, the feasibility and safety of combining photon IORT with ultrahypofractionated WBI. METHODS: Patients diagnosed with low-risk early BC candidates for BCS were included in this prospective study. IORT was administered at a dose of 20 Gy to the surface's applicator, and WBI was administered 3-5 weeks after surgery at a total dose of 26 Gy in five consecutive days. RESULTS: From July 2020 to December 2022, seventy-two patients diagnosed with low-risk early BC and treated in our institution were included in this prospective study. All patients completed the proposed treatment, and no severe acute or late grade 3 toxicity was observed 3 and 12 months after WBI, respectively. CONCLUSIONS: Our results confirm for the first time that the combination of ultrafractionation WBI and photon-IORT after BCS is a feasible and safe option in patients with early BC.

Identification of Peripheral Fatigue through Exercise-Induced Changes in Muscle Contractility.

The aim of this study was to assess whether tensiomyography is a tool sensitive enough to detect peripheral fatigue. Twenty-six strength-trained men were split into two groups: 1) a fatigued group (FG), who performed a full-squat (SQ) standardized warm-up plus 3 x 8 SQs with 75% 1RM with a 5-min rest interval, and 2) a non-fatigued group (NFG), who only did the SQ standardized warm-up. The countermovement jump (CMJ), maximal isometric force (MIF) in the SQ at 90º knee flexion, and TMG in vastus medialis (VM) and vastus lateralis (VL) muscles were assessed pre- and post-protocols. Data were analyzed through mixed ANOVA, logistic regression analysis, and receiver-operating curves. There were significant group x time interactions (p < 0.01) for CMJ height, MIF, maximal radial displacement (Dm), and radial displacement velocity (Vrd90) since the FG acutely decreased in these variables, while no significant changes were observed for the NFG. The logistic regression showed a significant model for detecting fatigue, whether it used the CMJ or MIF, with only the relative change in VL-Vrd90 as a fatigue predictor. The determination of the area under the curve showed that Dm and Vrd90 had good to excellent discriminative ability. Dm and Vrd90 are sensitive to detect fatigue in VL and VM muscles in resistance training contexts.

Next-generation BCMA-targeted chimeric antigen receptor CARTemis-1: the impact of manufacturing procedure on CAR T-cell features.

PURPOSE: CAR therapy targeting BCMA is under investigation as treatment for multiple myeloma. However, given the lack of plateau in most studies, pursuing more effective alternatives is imperative. We present the preclinical and clinical validation of a new optimized anti-BCMA CAR (CARTemis-1). In addition, we explored how the manufacturing process could impact CAR-T cell product quality and fitness. METHODS: CARTemis-1 optimizations were evaluated at the preclinical level both, in vitro and in vivo. CARTemis-1 generation was validated under GMP conditions, studying the dynamics of the immunophenotype from leukapheresis to final product. Here, we studied the impact of the manufacturing process on CAR-T cells to define optimal cell culture protocol and expansion time to increase product fitness. RESULTS: Two different versions of CARTemis-1 with different spacers were compared. The longer version showed increased cytotoxicity. The incorporation of the safety-gene EGFRt into the CARTemis-1 structure can be used as a monitoring marker. CARTemis-1 showed no inhibition by soluble BCMA and presents potent antitumor effects both in vitro and in vivo. Expansion with IL-2 or IL-7/IL-15 was compared, revealing greater proliferation, less differentiation, and less exhaustion with IL-7/IL-15. Three consecutive batches of CARTemis-1 were produced under GMP guidelines meeting all the required specifications. CARTemis-1 cells manufactured under GMP conditions showed increased memory subpopulations, reduced exhaustion markers and selective antitumor efficacy against MM cell lines and primary myeloma cells. The optimal release time points for obtaining the best fit product were > 6 and < 10 days (days 8-10). CONCLUSIONS: CARTemis-1 has been rationally designed to increase antitumor efficacy, overcome sBCMA inhibition, and incorporate the expression of a safety-gene. The generation of CARTemis-1 was successfully validated under GMP standards. A phase I/II clinical trial for patients with multiple myeloma will be conducted (EuCT number 2022-503063-15-00).