Search Results (40,086)

Opioid peptide hybrids are multifunctional molecules in which an opioid pharmacophore is covalently integrated with a second opioid or non-opioid pharmacophore within a single molecular entity. Their development is driven by a major challenge in analgesic pharmacotherapy: although μ-opioid receptor (MOR) agonists remain among the most effective agents for the treatment of moderate-to-severe pain, their therapeutic use is limited by adverse effects and risks associated particularly with prolonged or high-dose exposure, including tolerance, constipation, respiratory depression, physical dependence, and abuse liability. Especially, chronic and neuropathic pain involves complex interactions among multiple receptor systems, neurotransmitter networks, and intracellular signaling pathways. Accordingly, hybrid peptide ligands provide a rational multitarget strategy aimed at achieving analgesia through the coordinated modulation of complementary pharmacological targets rather than selective modulation of a single receptor system. This approach may enhance analgesic efficacy and potentially improve the therapeutic profile of opioid-based treatments by reducing some of the dose-limiting adverse effects associated with conventional opioid analgesics. In this review, we discuss the functional and pharmacological interactions between opioid receptors and other receptor systems involved in pain perception and modulation, with emphasis on those for which peptide-based hybrid ligands with demonstrated antinociceptive activity have been developed. Full article

Coolants containing glycols, corrosion inhibitors and anti-foaming additives pose a significant environmental risk due to their limited susceptibility to natural degradation. At the same time, glycols are valuable raw materials widely used across industrial sectors, and global consumption of ethylene glycol, the principal component of most coolants, has been steadily increasing. Microbial biodegradation offers an economically and environmentally attractive route for treating spent coolants. In this study, fourteen environment-derived strains from a culture collection, thirteen bacteria and one yeast, were screened for the ability to grow on two chemically distinct industrial coolant matrices: an unused, ethylene-glycol-based product (Petrygo Q NEW) and a propylene-glycol-dominated spent fluid drained from an engine cooling system. Six strains (AC2/2, B3J, 5A, B9F, B16B and 17E) showing the highest growth potential were subjected to adaptive laboratory evolution (ALE) by serial passaging for ten transfers in a minimal medium containing 1.5 g L⁻¹ yeast extract, in which the coolant provided the principal carbon and energy source. Growth dynamics of evolved and ancestral strains were compared by microplate cultivation, glycol depletion was quantified by high-performance liquid chromatography (HPLC) in shake-flask cultures, and tolerance was assessed by spot assays. Adaptation was strain-specific and was generally more pronounced on the spent, propylene-glycol-dominated fluid than on the unused, ethylene-glycol-based product. After selection, removal of ethylene glycol from the spent fluid within 96 h increased from 33.3% to 79.7% for Wickerhamomyces anomalus B16B and from 24.8% to 60.1% for Bacillus sp. B9F, while Pseudomonas sp. AC2/2 depleted 64.3% of the propylene glycol present that is 25.6 g L⁻¹ and the largest mass removed from either matrix. In the unused, ethylene-glycol-based product, removal also increased after ALE, reaching 10.9 g L⁻¹ for AC2/2 from an initial load of about 50 g L⁻¹, but none of these differences were significant. To the best of our knowledge, this is the first application of ALE to an intact commercial coolant and to a spent fluid drained from an engine cooling system, and it demonstrates that non-modified environmental isolates can be improved for the treatment of this hazardous waste stream without genetic modification. Full article

Soil salinization poses a serious threat to global food security, and screening for salt-tolerant soybean germplasm is an effective approach for the efficient utilization of saline–alkali lands. In this study, 116 soybean germplasm accessions developed by Heze Academy of Agricultural Sciences were used as materials. Initial screening for salt tolerance was conducted at the germination stage; then, tolerant accessions were selected and further validated under saline–alkali field conditions at maturity. Comprehensive evaluation was performed via principal component analysis and the membership function method, alongside correlation analysis of agronomic traits. A concentration of 0.5% NaCl (m/v) was determined to be the optimal screening concentration for seed germination, based on which seven strong salt-tolerant materials were selected. Field validation showed that grain weight per plant was strongly correlated with yield under salt stress among the seven accessions tested. The results indicated that Hedou 29 and Hedou 12 exhibited outstanding performance under both evaluation methods. Hedou 29 and Hedou 12 can serve as promising parental materials for salt-tolerant soybean breeding. This study provides empirical data support for breeding salt-tolerant soybean varieties and offers potential cultivar options for soybean production on saline–alkali soils in the Huang-Huai-Hai region. Full article

Perennial plant ecotypes exhibit adaptive functional traits associated with abiotic stress tolerance linked to their origin. This study hypothesized that F. gracillima displays ecotypic variation that employs different shoot–root compensation mechanisms to sustain plant growth and development. A growth chamber experiment was conducted to investigate the adaptive traits of F. gracillima accessions derived from seeds collected in steppe and transition zones. Destructive sampling was performed at six development stages, while non-destructive measurements were taken biweekly (roots) and every 2 days (shoots) from six pots per accession. The development stages were (i) seedling, (ii) one fully expanded leaf, (iii) two fully expanded leaves, (iv) three fully expanded leaves, (v) early senescence, and (vi) late senescence (one fully senesced leaf). A factorial design with six developmental stages × two accessions × six replicates was used. The steppe accession had a greater fine-root length percentage, a smaller root diameter, longer single roots, fewer roots, a slower rhizochron (i.e., a slower root appearance rate) and a faster leaf phyllochron (i.e., a faster leaf appearance rate). Phenotypic differences between accessions support the existence of ecotypic variation. The steppe accession combined acquisitive and conservative traits, indicating multidimensional trait variation rather than a single acquisitive–conservative strategy. Additionally, asynchronous leaf and root tissue appearance rates suggest partial decoupling between above- and belowground development. Full article

Background: This study aimed to explore first-trimester metabolic profiles associated with gestational diabetes mellitus (GDM) and its glycemic subtypes. Methods: This nested case–control study included 90 women with GDM, comprising 30 with isolated fasting hyperglycemia (IFH), 30 with isolated post-load hyperglycemia (IPH), and 30 with combined hyperglycemia (CH), together with 30 women with normal glucose tolerance (NGT). Untargeted UHPLC-MS metabolomic profiling was performed on fasting plasma samples collected during the first trimester. Exploratory metabolic features were compared between GDM or its subtypes and NGT, and Spearman correlation analyses were performed to examine associations between candidate metabolic features and maternal fasting blood glucose (FBG), BMI, thyroid-related parameters, parity, education, and gestational weight gain. Exploratory pathway analyses were conducted to characterize potentially related metabolic processes. Results: At the exploratory threshold of VIP > 1 and nominal p < 0.05, 107 candidate metabolic features were observed in the GDM vs. NGT comparison, with 89, 76, and 123 candidate features observed in the IFH vs. NGT, IPH vs. NGT, and CH vs. NGT comparisons, respectively. These candidate features were mainly annotated as organoheterocyclic compounds and lipids and lipid-like molecules, with differences in chemical-class distributions across subtype comparisons. Organosulfur-related annotations were observed among the IFH candidate features, whereas alkaloid-related annotations were observed among the CH candidate features. No individual feature remained statistically significant after multiple-testing correction. Correlation analyses identified FDR-adjusted associations between selected candidate metabolic features and maternal FBG, BMI, and thyroid-related parameters. Exploratory pathway mapping highlighted processes related to lipid, amino acid, carbohydrate, and nucleotide metabolism. Conclusions: This exploratory study suggests that first-trimester plasma metabolic patterns may differ among women who subsequently develop different glycemic subtypes of GDM. The observed candidate features, clinical correlations, and pathway-level patterns provide hypotheses regarding metabolic heterogeneity in GDM but should not be considered validated biomarkers or subtype-specific metabolic signatures. Further studies using targeted metabolomics and larger independent cohorts are needed to confirm these observations. Full article

Background: Diabetes in males leads to hyperglycemia-induced oxidative stress and inflammation in the testis, resulting in apoptosis. Diabetes-induced testicular impairment has been linked to the implication with the gut–brain axis. Sodium butyrate, a product of the gut microbiota fermentation process, has been targeted for its anti-diabetic, anti-inflammatory, and antioxidative functions. This research, therefore, explored sodium butyrate as a therapeutic potential intervention in mitigating diabetes-induced testicular dysfunction. Methods: Thirty-five male rats were randomly assigned to five groups after diabetes was confirmed: healthy control (CON), sodium butyrate-treated (SBUT; 200 mg/kg orally), diabetic control (T1DM; 50 mg/kg STZ intraperitoneally), diabetes + sodium butyrate (T1DM + SBUT), and diabetes + insulin (T1DM + INSL, 0.9 I.U/100 g/day). Body weight, testicular weight, glucose homeostasis (fasting blood sugar, oral glucose tolerance, and glycated hemoglobin), lipid profile, testosterone level, sperm analysis, histopathology of the testis, and anti-apoptotic markers (B-cell lymphoma-2 (Bcl-2), Bcl-associated protein X (Bax), and Caspase-3) were all assessed. Results: Along with elevated blood glucose and glycated hemoglobin levels, diabetic rats showed a notable decrease in body weight, testicular mass, gonadosomatic index, sperm count, motility, viability, and normal morphology. Elevated Bax and Caspase-3 expression with reduced Bcl-2 were observed alongside testicular fibrosis, accumulation of collagen, and carbohydrate-rich substances. Sodium butyrate treatment, by downregulating Bax and Caspase-3 and upregulating Bcl-2, conserved testicular histoarchitecture, restored sperm quality, controlled apoptotic signaling, and markedly improved metabolic indices. Conclusions: Sodium butyrate displayed a protective role in the testis in diabetic conditions via the modulation of hyperglycemia-induced apoptosis, identifying this as a potential therapeutic intervention in diabetes-induced testicular dysfunction. Full article

Background/Objectives: The optimal dialysate calcium concentration in maintenance hemodialysis remains uncertain because reducing calcium exposure may limit calcium loading but can also stimulate parathyroid hormone secretion and impair intradialytic cardiovascular stability. We evaluated randomized evidence across bone, mineral metabolism, vascular, and acute safety outcomes. Methods: PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), and Scopus were searched from database inception through 10 July 2026, with targeted citation and publication-status updating through 1 August 2026. Randomized parallel, crossover, factorial, and multi-period trials comparing dialysate calcium concentrations in adults receiving hemodialysis or hemodiafiltration were eligible. Acute and chronic outcomes were analyzed separately. Pooled estimates used inverse-variance random-effects models with DerSimonian–Laird estimation and modified Hartung–Knapp confidence intervals. Results: Twenty-four randomized parent trials were included. Lower dialysate calcium reduced end-of-dialysis ionized calcium (paired mean difference, −0.193 mmol/L; 95% CI, −0.258 to −0.128), with substantial heterogeneity. Point estimates for chronic parathyroid hormone and total alkaline phosphatase were higher and serum calcium lower, but all confidence intervals crossed the null. No clear effects were demonstrated for phosphate, calcium–phosphate product, lumbar bone mineral density, coronary artery calcification, or carotid intima–media thickness. Acute parathyroid hormone, blood pressure, calcium-balance, and QTc estimates suggested greater parathyroid stimulation, lower hemodynamic measures, less calcium gain, and longer QTc with lower calcium, but were imprecise. Adverse events were unsuitable for pooling. Conclusions: Lower dialysate calcium consistently lowers postdialysis ionized calcium, but its long-term skeletal and vascular effects remain uncertain. No single concentration appears universally optimal; prescription should be individualized according to mineral metabolism phenotype, cardiovascular tolerance, dialysis modality, and concomitant therapy. Full article

A stable chromosome count does not imply a static genome. Oryza species have largely retained a basic chromosome number of 12, yet most rearrangements are described against extant references, making ancestral and derived orientations difficult to distinguish. We reconstructed an ancestral Oryza karyotype (AOK) containing 12 chromosomes and 23,010 ordered genes from 24 chromosome-level genome assemblies representing 34 ingroup genome/subgenome units. Unlike a modern reference, the AOK provides gene-order polarity, allowing rearrangements detected in different species and population panels to be compared in the same evolutionary direction. AOK-polarized analysis of 400 rice assemblies revealed structural change at two scales. Across species, the derived allotetraploid karyotypes of Oryza alta and Oryza grandiglumis were parsimoniously accounted for by three reciprocal translocations. Within rice populations, four principal inversion-associated loci showed contrasting lineage distributions. The most complex locus, on chromosome 6, comprised nested structural haplotypes that were unevenly distributed among rice populations and associated with published variation in seedling cold tolerance. These findings show how lineage-specific chromosome exchanges and polymorphic inversion complexes have reshaped a numerically conserved karyotype. More broadly, an ancestral gene-order reference links deep karyotype evolution with standing structural diversity and provides a framework for tracing the direction of chromosome rearrangements during rice diversification. Full article

Postprandial hyperglycemia can be modified before absorbed glucose reaches the circulation. Plant-derived compounds may slow starch hydrolysis through α-amylase and intestinal α-glucosidases, stimulate glucagon-like peptide-1 (GLP-1) release, or preserve incretin activity through dipeptidyl peptidase-4 (DPP-4) inhibition. This critical narrative review integrates these mechanisms around intestinal exposure, substrate selectivity, and human evidence. Flavonoids show structure-dependent and time-dependent inhibition of carbohydrate-hydrolyzing enzymes, but results vary markedly between yeast, rodent, and human enzyme systems. Iminosugar-rich mulberry preparations and thiosugar-containing Salacia extracts provide the strongest chemistry-to-clinic examples, including randomized trials that reduced postprandial glucose or HbA1c. Preclinical studies suggest that berberine may link bitter-taste-receptor-mediated GLP-1 secretion with local intestinal DPP-4 effects, whereas mangiferin, flavonol glycosides, anthocyanins, and food-derived peptides remain supported mainly by preclinical studies. In vitro potency alone is insufficient: meal composition, enzyme source, luminal concentration, metabolism, product standardization, gastrointestinal tolerance, and incretin measurements determine translational value. Candidate prioritization requires defined chemistry, achievable exposure, and product-specific human validation; acute effects do not establish durable benefit or human target engagement. Full article

Background/Objectives: Stable angina is a significant health issue in Egypt, often showing poor responses to standard treatments. This study examines the effectiveness and safety of early combination therapy with trimetazidine and either a β-blocker or a calcium channel blocker (CCB) among Egyptian patients with stable angina. Methods: This sub-analysis of the Egyptian cohort from the COMBINE Angina study included patients with stable angina (CCS class II–III) who remained symptomatic after 2–4 weeks of β-blocker or CCB monotherapy. Patients received trimetazidine 35 mg modified-release twice daily as an add-on treatment for 4 months. The primary outcome was the Seattle Angina Questionnaire (SAQ-7) summary score, with secondary outcomes including SAQ-7 domain scores, CCS class, frequency of angina attacks, nitrate use, treatment satisfaction, adherence, and safety. Results: In the global COMBINE study involving 578 patients, the Egyptian cohort had 138 participants with an average age of 58.3 years. The SAQ-7 summary score improved from 42.2 at baseline to 76.8 at month 4 (mean change 34.6 points, 95% CI 31.3 to 38.0; p < 0.0001). All 138 patients contributed data at every visit for the SAQ-7 summary score. Patients in CCS class I increased from 0% to 56.5%, weekly angina attacks fell from 5.0 to 1.7 (p < 0.0001), and short-acting nitrate use decreased from 2.9 to 1.0 doses per week (p < 0.0001). Patient satisfaction was about 75%, and physician satisfaction reached 83% by month 4. Medication adherence also improved (MARS-5 score: 20.8 to 22.7), and two non-serious, treatment-related adverse events (nausea and somnolence) were reported in a single patient (0.7%), with no serious or fatal events. Conclusions: In Egyptian patients with stable angina, implementing an early combination strategy incorporating trimetazidine with first-line β-blocker or CCB therapy was associated with clinically meaningful improvements in angina symptoms, functional status, and quality of life, with good tolerability and high satisfaction. As the study was observational and single-arm, these findings are provisional and require confirmation in further long-term controlled studies. Full article

Background and Objectives: Modulation of the gut–liver axis with non-viable microbial components is a promising approach to correct metabolic disorders. The aim of the study was to evaluate the short-term efficacy and safety of the postbiotic lysate Lactobacillus rhamnosus DV-NRRL B-68023 on non-invasive measures of hepatic steatosis, transaminase activity, and anthropometric parameters in patients with MASLD. Materials and Methods: In a randomized, double-blind, placebo-controlled trial (NCT06352697), 52 adults were assigned 1:1 to receive the postbiotic Del-Immune V^® Extra (100 mg twice daily; n = 26) or placebo (n = 26) for 3 months followed by a 3-month follow-up without treatment. The registered co-primary endpoints were FLI, HSI, and TyG. Additionally, transaminases, lipid parameters, hs-CRP, and body composition indices were assessed. Results: In the ITT analysis (n = 52), FLI showed a nominal time-by-treatment interaction (p = 0.049), with a between-group difference in change at month 3 of −7.20 points (95% CI: −12.95 to −1.46). HSI and TyG did not differ significantly between groups. In exploratory ITT analyses, waist circumference showed a significant time-by-treatment interaction (p = 0.003), whereas the interaction for visceral fat was not significant (p = 0.079). ALT and AST decreased significantly within the postbiotic group, but the corresponding time-by-treatment interactions were not significant (p = 0.340 and p = 0.111, respectively). Lipid parameters and hs-CRP did not differ significantly between groups. All adverse events were mild and self-limiting. Conclusions: Three months of Lactobacillus rhamnosus lysate DV-NRRL B-68023 was well tolerated. Among the three registered co-primary surrogate indices, only FLI showed a nominal between-group difference; HSI and TyG did not. An exploratory reduction in waist circumference was observed, whereas the ALT and AST changes were not significantly different from placebo. These findings warrant confirmation in larger studies using direct liver assessments and longer follow-up. Full article

Food-associated microorganisms represent a diverse reservoir of bacterial strains with functional traits potentially relevant to host–microbiome interactions, stress resilience, metabolic processes, and microbial competition. In this study, we performed a multi-omics characterization of food-origin bacterial isolates to identify a potential candidate strain for further studies on microbiome–microgreens interactions. Over one hundred bacterial isolates were initially recovered from various food products and subjected to molecular screening, followed by whole-genome sequencing, metabolic profiling, transcriptomic chcracterisation and morphological analysis of selected strains. Comparative characterization revealed significant differences among the strains. Among the tested isolates, strain B107/23, identified as Priestia megaterium (formerly Bacillus megaterium), had the highest number of genes associated with stress responses, nutrient uptake, plant growth-promoting traits, and colonization mechanisms. Phenotypic characterization later demonstrated high metabolic flexibility and a low substrate stress index, while transcriptomic profiling revealed the expression of genes associated with stress responses and metabolic activity. Overall, the integration of genomic, phenotypic, and transcriptomic results distinguished B107/23 as the most promising candidate among the tested isolates and revealed the molecular traits potentially significant to interactions between the microbe and the host. These findings provide a basis for the validation of the selected strain in microgreens systems, including studies addressing plant stress resilience and post-harvest quality. Full article

Background: Protein phosphatase 2A (PP2A) is a conserved serine/threonine phosphatase that plays crucial roles in stress responses, yet its function in strawberry (Fragaria spp.) remains largely uncharacterized. This study aimed to characterize the PP2A gene family in octoploid strawberry and to investigate its involvement in ALA-induced salt tolerance. Methods: We identified PP2A genes in the octoploid strawberry ‘Benihoppe’ genome and classified them into scaffold (A), regulatory (B55, B56, B″), and catalytic (C) subunit families. Segmental duplication and selection pressure were analyzed using Ka/Ks. Time-course RNA-seq was performed under NaCl and ALA treatments. Physiological assays measured SOD and CAT activities, O₂•⁻ and MDA accumulation, and PP2A activity. Cantharidin was used to pharmacologically inhibit PP2A. Results: Seventy-five PP2A genes were identified. Segmental duplication was the primary driver of PP2A family expansion (70/75 genes), with all duplicated pairs under strong purifying selection (mean Ka/Ks = 0.138). Time-course RNA-seq analysed with DESeq2 identified three B56-subfamily PP2A genes as differentially expressed between NaCl and NaCl + ALA at 24 h (FDR < 0.05), the most strongly affected being FaPP2AB′η-5; in contrast, several C4 catalytic subunits were suppressed by salt stress. This ALA-responsive induction declined sharply at 48 h and 72 h. Physiological assays demonstrated that ALA significantly enhanced SOD and CAT activities while reducing O₂•⁻ and MDA accumulation under NaCl stress, and ALA also elevated PP2A activity. Cantharidin largely attenuated both the ALA-induced increase in PP2A activity and ALA-mediated antioxidant protection. Conclusions: This study provides a comprehensive characterization of the strawberry PP2A gene family and indicates that PP2A activity contributes to ALA-induced salt tolerance, revealing a functional link between ALA signaling and PP2A-mediated antioxidant defense. Full article

Solder joints in aerospace, nuclear, and defense electronics are increasingly exposed to ionizing radiation, which creates serious reliability issues. Despite its importance, a comprehensive understanding of the underlying mechanisms and how they vary across radiation types remains lacking. This systematic literature review synthesizes 24 peer-reviewed studies (2000–2025) to evaluate radiation-induced microstructural evolution and mechanical degradation in Sn-based solder alloys. Following PRISMA guidelines, data were analyzed across gamma, electron, proton, neutron, and alpha irradiation, covering Sn–Pb, SAC305, AuSn20, SnBi, and related systems. Gamma irradiation predominantly accelerates interfacial diffusion kinetics, resulting in IMC thickening, oxidation, and shear strength reductions. However, the effects are dose-dependent, where low doses temporarily harden the material, while higher doses make it brittle. Lead-free SAC305 alloys exhibit greater radiation sensitivity than Sn–Pb systems, showing accelerated IMC growth, defect accumulation, and lattice instability. Proton and neutron irradiation induce displacement-dominated damage, including defect clustering and Kirkendall voiding. Combination of electron irradiation and thermal cycling produces synergistic degradation exceeding single-stressor effects. By integrating experimental findings with atomistic and multiscale modeling insights, this review links defect generation, interfacial instability, and mechanical degradation using established radiation-enhanced diffusion (RED) principles. The results clarify radiation-type-dependent damage mechanisms, highlight alloy-specific tolerance differences, and identify critical gaps in multi-stressor testing and predictive lifetime modeling. The mechanistic insights presented here serve as a foundation for optimizing solder alloy design and strengthening qualification procedures for radiation-prone electronic applications. Full article

Background/Objectives: Gestational diabetes mellitus (GDM) is associated with increased short- and long-term risks for both mother and child. Screening and treatment between 24 and 30 weeks’ gestation reduces adverse pregnancy outcomes, while emerging evidence suggests that earlier diagnosis and treatment (<20 weeks’) in high-risk populations may further improve neonatal outcomes. Currently, self-monitoring of blood glucose (SMBG) remains the standard of care for management but provides only intermittent glycemic data and limited insight into overall glucose patterns. Real-time continuous glucose monitoring (rt-CGM) has transformed management in pregnancies complicated by type 1 diabetes but has shown conflicting results in GDM; it is thus unclear whether similar benefits may extend to women with GDM, including women with early GDM. Methods: The Continuous Glucose Monitoring for Women With Gestational Diabetes (CORDELIA) study is an ongoing, large, open-label, multicenter randomized controlled trial conducted across 14 centers in Belgium and two centers in Australia. Women diagnosed with GDM are randomized in a 1:1 ratio to either rt-CGM (intervention group) or standard care with SMBG (control group). Both women with early GDM diagnosed before 20 weeks’ gestation and those diagnosed between 24.0 and 29.6 weeks’ gestation are included. Participants attend the following visits: baseline visit at GDM diagnosis, an additional visit at 20.0–23.9 weeks’ (if early GDM), 31.0–33.6 weeks’ and 36.0–38.6 weeks’, and a postpartum oral glucose tolerance test (OGTT) assessment (6.0–23.6 weeks after delivery). At each visit, clinical assessment, HbA1c, and (blinded) CGM are evaluated, alongside validated patient-reported outcome questionnaires. The primary objective is to compare the incidence of a composite of adverse pregnancy outcomes between the rt-CGM and SMBG groups. The primary outcome is a composite of adverse pregnancy outcomes including preterm delivery <37 weeks, LGA [customized percentiles according to Gestation Related Optimal Weight chart (GROW)], neonatal hypoglycemia requiring intravenous dextrose, neonatal intensive care unit (NICU) admission > 24 h, neonatal respiratory distress, stillbirth or neonatal death, phototherapy, birth trauma, and shoulder dystocia. Secondary outcomes include maternal glycemia, insulin use, pregnancy and neonatal outcomes, glycemic variability, patient-reported outcomes, and prespecified secondary analyses according to timing of GDM diagnosis and maternal BMI. Trial Registration: ClinicalTrials.gov: NCT06310356. First posted: 15 March 2024. Full article