Local and global changes in cell density induce reorganisation of 3D packing in a proliferating epithelium.

Tissue morphogenesis is intimately linked to the changes in shape and organisation of individual cells. In curved epithelia, cells can intercalate along their own apicobasal axes, adopting a shape named 'scutoid' that allows energy minimization in the tissue. Although several geometric and biophysical factors have been associated with this 3D reorganisation, the dynamic changes underlying scutoid formation in 3D epithelial packing remain poorly understood. Here, we use live imaging of the sea star embryo coupled with deep learning-based segmentation to dissect the relative contributions of cell density, tissue compaction and cell proliferation on epithelial architecture. We find that tissue compaction, which naturally occurs in the embryo, is necessary for the appearance of scutoids. Physical compression experiments identify cell density as the factor promoting scutoid formation at a global level. Finally, the comparison of the developing embryo with computational models indicates that the increase in the proportion of scutoids is directly associated with cell divisions. Our results suggest that apico-basal intercalations appearing immediately after mitosis may help accommodate the new cells within the tissue. We propose that proliferation in a compact epithelium induces 3D cell rearrangements during development.

Using JADES NIRCam photometry to investigate the dependence of stellar mass inferences on the IMF in the early universe.

The detection of numerous and relatively bright galaxies at redshifts z > 9 has prompted new investigations into the star-forming properties of high-redshift galaxies. Using local forms of the initial mass function (IMF) to estimate stellar masses of these galaxies from their light output leads to galaxy masses that are at the limit allowed for the state of the Lambda Cold Dark Matter (ΛCDM) Universe at their redshift. We explore how varying the IMF assumed in studies of galaxies in the early universe changes the inferred values for the stellar masses of these galaxies. We infer galaxy properties with the spectral energy distribution (SED) fitting code Prospector using varying IMF parameterizations for a sample of 102 galaxies with photometry from the James Webb Space Telescope, JWST Advanced Deep Extragalactic Survey that are spectroscopically confirmed to be at [Formula: see text], with additional photometry from the JWST Extragalactic Medium Band Survey for twenty-one of the galaxies. We demonstrate that models with stellar masses reduced by a factor of three or more do not affect the modeled SED.

Top predator sea stars are the benthic equivalent to polar bears of the pelagic realm.

The marine pelagic compartment spans numerous trophic levels and consists of numerous reticulate connections between species from primary producers to iconic apex predators, while the benthic compartment is perceived to be simpler in structure and comprised of only low trophic level species. Here, we challenge this paradigm by illustrating that the benthic compartment is home to a subweb of similar structure and complexity to that of the pelagic realm, including the benthic equivalent to iconic polar bears: megafaunal-predatory sea stars.

Recurrent excision of a hAT-like transposable element in CmAPRR2 leads to the "shooting star" melon phenotype.

The external appearance of fruit commodities is an essential trait that has profound effects on consumer preferences. A natural melon variety, characterized by an uneven and patchy arrangement of dark green streaks and spots on the white-skinned rind, resembles shooting stars streaking across the sky; thus, this variety is called "Shooting Star" (SS). To investigate the mechanism underlying the SS melon rind pattern, we initially discovered that the variegated dark green color results from chlorophyll accumulation on the white skin. We then constructed a segregation population by crossing a SS inbred line with a white rind (WR) inbred line and used bulk segregant analysis (BSA) revealed that the SS phenotype is controlled by a single dominant gene, CmAPRR2, which has been previously confirmed to determine dark green coloration. Further genomic analysis revealed a hAT-like transposable element (TE) inserted in CmAPRR2. This TE in CmAPRR2 is recurrently excised from rind tissues, activating the expression of CmAPRR2. This activation promotes the accumulation of chlorophyll, leading to the variegated dark green color on the rind, and ultimately resulting in the SS rind phenotype. Therefore, we propose that the SS phenotype results from the recurrent excision of the hAT-like TE in CmAPRR2.

Single-cell RNA-sequencing analysis of early sea star development.

Echinoderms represent a broad phylum with many tractable features to test evolutionary changes and constraints. Here, we present a single-cell RNA-sequencing analysis of early development in the sea star Patiria miniata, to complement the recent analysis of two sea urchin species. We identified 20 cell states across six developmental stages from 8 hpf to mid-gastrula stage, using the analysis of 25,703 cells. The clusters were assigned cell states based on known marker gene expression and by in situ RNA hybridization. We found that early (morula, 8-14 hpf) and late (blastula-to-mid-gastrula) cell states are transcriptionally distinct. Cells surrounding the blastopore undergo rapid cell state changes that include endomesoderm diversification. Of particular import to understanding germ cell specification is that we never see Nodal pathway members within Nanos/Vasa-positive cells in the region known to give rise to the primordial germ cells (PGCs). The results from this work contrast the results of PGC specification in the sea urchin, and the dataset presented here enables deeper comparative studies in tractable developmental models for testing a variety of developmental mechanisms.

STMHCpan, an accurate Star-Transformer-based extensible framework for predicting MHC I allele binding peptides.

Peptide-major histocompatibility complex I (MHC I) binding affinity prediction is crucial for vaccine development, but existing methods face limitations such as small datasets, model overfitting due to excessive parameters and suboptimal performance. Here, we present STMHCPan (STAR-MHCPan), an open-source package based on the Star-Transformer model, for MHC I binding peptide prediction. Our approach introduces an attention mechanism to improve the deep learning network architecture and performance in antigen prediction. Compared with classical deep learning algorithms, STMHCPan exhibits improved performance with fewer parameters in receptor affinity training. Furthermore, STMHCPan outperforms existing ligand benchmark datasets identified by mass spectrometry. It can also handle peptides of arbitrary length and is highly scalable for predicting T-cell responses. Our software is freely available for use, training and extension through Github (https://github.com/Luckysoutheast/STMHCPan.git).

WMSA 2: a multiple DNA/RNA sequence alignment tool implemented with accurate progressive mode and a fast win-win mode combining the center star and progressive strategies.

Multiple sequence alignment is widely used for sequence analysis, such as identifying important sites and phylogenetic analysis. Traditional methods, such as progressive alignment, are time-consuming. To address this issue, we introduce StarTree, a novel method to fast construct a guide tree by combining sequence clustering and hierarchical clustering. Furthermore, we develop a new heuristic similar region detection algorithm using the FM-index and apply the k-banded dynamic program to the profile alignment. We also introduce a win-win alignment algorithm that applies the central star strategy within the clusters to fast the alignment process, then uses the progressive strategy to align the central-aligned profiles, guaranteeing the final alignment's accuracy. We present WMSA 2 based on these improvements and compare the speed and accuracy with other popular methods. The results show that the guide tree made by the StarTree clustering method can lead to better accuracy than that of PartTree while consuming less time and memory than that of UPGMA and mBed methods on datasets with thousands of sequences. During the alignment of simulated data sets, WMSA 2 can consume less time and memory while ranking at the top of Q and TC scores. The WMSA 2 is still better at the time, and memory efficiency on the real datasets and ranks at the top on the average sum of pairs score. For the alignment of 1 million SARS-CoV-2 genomes, the win-win mode of WMSA 2 significantly decreased the consumption time than the former version. The source code and data are available at https://github.com/malabz/WMSA2.

Designer Spin Models in Tunable Two-Dimensional Nanographene Lattices.

Motivated by recent experimental breakthroughs, we propose a strategy for designing two-dimensional spin-lattices with competing interactions that lead to nontrivial emergent quantum states. We consider S = 1/2 nanographenes with C3 symmetry as building blocks, and we leverage the potential to control both the sign and the strength of exchange with first neighbors to build a family of spin models. Specifically, we consider the case of a Heisenberg model in a triangle-decorated honeycomb lattice with competing ferromagnetic and antiferromagnetic interactions whose ratio can be varied in a wide range. On the basis of the exact diagonalization of both Fermionic and spin models, we predict a quantum phase transition between a valence bond crystal of spin singlets with triplon excitations living in a Kagomé lattice and a Néel phase of effective S = 3/2 in the limit of dominant ferromagnetic interactions.

Intercalating Architecture for the Design of Charge Density Wave in Metallic MA2Z4 Materials.

We present a novel approach to induce charge density waves (CDWs) in metallic MA2Z4 materials, resembling the behavior observed in transition metal dichalcogenides (TMDCs). This method leverages the intercalating architecture to maintain the same crystal field and Fermi surface topologies. Our investigation reveals that CDW instability in these materials arises from electron-phonon coupling (EPC) between the d band and longitudinal acoustic (LA) phonons, mirroring TMDC's behavior. By combining α-MA2Z4 with 1H-MX2 materials in a predictive CDW phase diagram using critical EPC constants, we demonstrate the feasibility of extending CDW across material families with comparable crystal fields and reveal the crucial role in CDW instability of the competition between ionic charge transfer and electron correlation. We further uncover a strain-induced Mott transition in ß2-NbGe2N4 monolayer featuring star-of-David patterns. This work highlights the potential of intercalating architecture to engineer CDW materials, expanding our understanding of CDW instability and correlation physics.

A gastrointestinal locally activating Janus kinase inhibitor to treat ulcerative colitis.

In this study, we integrated machine learning (ML), structure-tissue selectivity-activity-relationship (STAR), and wet lab synthesis/testing to design a gastrointestinal (GI) locally activating JAK inhibitor for ulcerative colitis treatment. The JAK inhibitor achieves site-specific efficacy through high local GI tissue selectivity while minimizing the requirement for JAK isoform specificity to reduce systemic toxicity. We used the ML model (CoGT) to classify whether the designed compounds were inhibitors or noninhibitors. Then we used the regression ML model (MTATFP) to predict their IC50 against related JAK isoforms of predicted JAK inhibitors. The ML model predicted MMT3-72, which was retained in the GI tract, to be a weak JAK1 inhibitor, while MMT3-72-M2, which accumulated in only GI tissues, was predicted to be an inhibitor of JAK1/2 and TYK2. ML docking methods were applied to simulate their docking poses in JAK isoforms. Application of these ML models enabled us to limit our synthetic efforts to MMT3-72 and MMT3-72-M2 for subsequent wet lab testing. The kinase assay confirmed MMT3-72 weakly inhibited JAK1, and MMT3-72-M2 inhibited JAK1/2 and TYK2. We found that MMT3-72 accumulated in the GI lumen, but not in GI tissue or plasma, but released MMT3-72-M2 accumulated in colon tissue with minimal exposure in the plasma. MMT3-72 achieved superior efficacy and reduced p-STAT3 in DSS-induced colitis. Overall, the integration of ML, the structure-tissue selectivity-activity-relationship system, and wet lab synthesis/testing could minimize the effort in the optimization of a JAK inhibitor to treat colitis. This site-specific inhibitor reduces systemic toxicity by minimizing the need for JAK isoform specificity.

Augmenting the Unites States transplant registry with external mortality data: A moving target ripe for further improvement.

The Organ Procurement and Transplantation Network conducts a robust death verification process when augmenting the United States transplant registry with external sources of data. Process enhancements added over 35,000 externally verified deaths across waitlist candidates and transplant recipients for all organs beginning in April 2022. Ninety-four percent of added posttransplant deaths occurred beyond 5 years posttransplant, and over 74% occurred beyond 10 years. Deceased donor solid organ recipients transplanted from January 1, 2010, through October 31, 2020, were analyzed from January and July 2022 Organ Procurement and Transplantation Network Standard Transplant Analysis and Research and the Scientific Registry of Transplant Recipients Standard Analysis Files to quantify the impact of including vs excluding unverified deaths (not releasable to researchers) on posttransplant patient survival estimates. Across all organs, 1- and 5-year posttransplant survival rates were not substantially impacted; meaningful differences were observed in 10-year survival among kidney recipients. These findings bear important implications for anyone who utilized transplant registry data to examine long-term outcomes prior to the updated verification process. Users of transplant surveillance data should interpret results of long-term outcomes cautiously, particularly differences across subpopulations, and the transplant community should identify ways to improve data quality and minimize the reporting burden on transplant institutions.

Trends in the healthiness and nutrient composition of packaged products sold by major food and beverage companies in New Zealand 2015 to 2019.

BACKGROUND: Dietary risk factors are the leading cause of death globally and in New Zealand (NZ). Processed packaged foods are prevalent in the food supply and contribute excess amounts of sodium, saturated fat, and sugar in diets. Improving the nutritional quality of these foods has the potential to reduce population chronic disease risk. We aimed to evaluate the healthiness using the Australasian Health Star Rating (HSR, from 0.5 to 5 stars, with 5 being the healthiest) and nutrient composition (sodium, saturated fat, and total sugar) of packaged products manufactured by the largest NZ-based food and beverage companies in NZ 2015-2019. This analysis relates to a larger study evaluating structured engagement with food companies to improve nutrition-related policies and actions. METHODS: Data was sourced from Nutritrack, a NZ-branded supermarket-sourced food composition database. The largest NZ-based companies from annual retail sales revenue (n = 35) were identified using 2019 Euromonitor data. All relevant products of the selected companies were extracted for analysis. Products included totalled 17,795 with a yearly range of 3462-3672 products. The primary outcome was a nutrient profile score estimated using HSR. Healthiness was defined as ≥ 3.5 stars. Secondary outcomes were sodium, total sugar, and saturated fat per 100 g/100 mL. All outcomes were assessed overall, by food company, and food category. Change over time was tested using linear mixed models, adjusting for major food categories and cluster effects of food companies controlling for multiple comparisons. Model-adjusted mean differences between years were estimated with 95% confidence intervals. RESULTS: There was a small statistically significant increase in mean HSR between 2015 and 2019 (0.08 [0.15,0.01], p = 0.024). Mean total sugar content decreased over the same period (0.78 g/100 g [0.08,1.47], p = 0.020), but there were no significant changes in mean sodium or saturated fat contents. Seven of the 13 categories showed small increases in mean HSR (0.1-0.2). Most categories (9/13) exhibited a reduction in mean total sugar content. CONCLUSIONS: Between 2015 and 2019, there were slight improvements in the nutritional quality of selected packaged foods and drinks in NZ. Much more substantive changes are needed to address the health-related burden of unhealthy diets, supported by stronger government action and less reliance on voluntary industry initiatives.

Gas-Controlled Self-Assembly of Metallacycle-Cored Supramolecular Star Polymer with Tunable Antibacterial Activity.

Herein, a three-armed amphiphilic metallacycle-cored star supramolecular polymer (Por-MOM-PDMAEMA) has been designed and synthesized via highly efficient post-assembly polymerization. This star polymer is further self-assembled into nanoparticles of different sizes depending upon the experimental conditions. The gas-controlled morphology transformation and tunable antibacterial activities of Por-MOM-PDMAEMAis systematically investigated and compared with metallacycle (MOM). The superior antibacterial activity of Por-MOM-PDMAEMA against multidrug-resistant P. aeruginosa implies that the presence of photodynamic photosensitizer (Por) and cationic polymer chain will significantly enhance antibactericidal activity, which is mainly attributed to the synergistic effect of photosensitizer and polymer chain linked in one metallacycle core. By leveraging the unique properties of metallacycle and their dynamic response to gaseous stimuli, the antibacterial properties of the Por-MOM-PDMAEMA can be finely tuned in response to gas triggers.

The impact of acute low salinity stress on Antarctic echinoderms.

Climate change is causing increased coastal freshening in Antarctica, leading to reduced salinity. For Antarctica's endemic echinoderms, adapted to the stable polar environment, the impact of rapid reductions in coastal salinity on physiology and behaviour is currently unknown. Six common Antarctic echinoderms (the sea urchin Sterechinus neumayeri; the sea star Odontaster validus; the brittle star Ophionotus victoriae; and three sea cucumbers Cucumaria georgiana, Echinopsolus charcoti and Heterocucumis steineni), were directly transferred from ambient salinity (34.5‰) to a range of salinity dilutions (29-9‰) for 24 h. All species showed reduced activity and the establishment of a temporary osmotic gradient between coelomic fluid and external seawater. Most species exhibited a depression in oxygen consumption across tolerated salinities; however, at very low salinities that later resulted in mortality, oxygen consumption increased to levels comparable to those at ambient. Low salinity tolerance varied substantially between species, with O. victoriae being the least tolerant (24 h LC50 (lethal for 50% of animals) = 19.9‰) while E. charcoti and C. georgiana demonstrated the greatest tolerance (24 h LC50 = 11.5‰). These findings demonstrate the species-specific response of Antarctica's endemic echinoderms to short-term hypoosmotic salinity events, providing valuable insight into this phylum's ability to respond to an underreported impact of climate change.

TGF-ß1 and TGF-ß3, but not TGF-ß2, are upregulated in the ovaries of ovarian hyperstimulation syndrome†.

Ovarian hyperstimulation syndrome (OHSS) is a life-threatening and potentially fatal complication during in vitro fertilization treatment. The levels of transforming growth factor-ß1 (TGF-ß1) are upregulated in human follicular fluid and granulosa-lutein cells (hGL) of OHSS patients and could contribute to the development of OHSS by downregulating steroidogenic acute regulatory protein (StAR) expression. However, whether the same is true for the other two members of the TGF-ß family, TGF-ß2 and -ß3, remains unknown. We showed that all three TGF-ß isoforms were expressed in human follicular fluid. In comparison, TGF-ß1 was expressed at the highest level, followed by TGF-ß2 and TGF-ß3. Compared to non-OHSS patients, follicular fluid levels of TGF-ß1 and TGF-ß3 were significantly upregulated in OHSS patients. The same results were observed in mRNA levels of TGF-ß isoforms in hGL cells and ovaries of OHSS rats. In addition, StAR mRNA levels were upregulated in hGL cells of OHSS patients and the ovaries of OHSS rats. Treatment cells with TGF-ß isoforms downregulated the StAR expression with a comparable effect. Moreover, activations of SMAD3 signaling were required for TGF-ß isoforms-induced downregulation of StAR expression. This study indicates that follicular fluid TGF-ß1 and TGF-ß3 levels could be used as biomarkers and therapeutic targets for the OHSS.

Modulation of external and internal aluminum resistance by ALS3-dependent STAR1-mediated promotion of STOP1 degradation.

The ALMT1 transporter aids malate secretion, chelating Al3+ ions to form nontoxic Al-malate complexes, believed to exclude Al from the roots. However, the extent to which malate secreted by ALMT1 is solely used for the exclusion of Al3+ or can be reutilized by plant roots for internal Al tolerance remains uncertain. In our investigation, we explored the impact of malate secretion on both external and internal Al resistance in Arabidopsis thaliana. Additionally, we delved into the mechanism by which the tonoplast-localized bacterial-type ATP-binding cassette (ABC) transporter complex STAR1/ALS3 promotes the degradation of the Al resistance transcription factor STOP1 to regulate ALMT1 expression. Our study demonstrates that the level of secreted malate influences whether the Al-malate complex is excluded from the roots or transported into root cells. The nodulin 26-like intrinsic protein (NIP) subfamily members NIP1;1 and NIP1;2, located in the plasma membrane, coordinate with STAR1/ALS3 to facilitate Al-malate transport from root apoplasm to the symplasm and eventually to the vacuoles for the internal Al detoxification. ALS3-dependent STAR1 interacts with and promotes the degradation of STOP1, regulating malate exudation. Our findings demonstrate the dual roles of malate exudation in external Al exclusion and Al absorption for internal Al detoxification.

Severe adrenal insufficiency in six neonates with normal newborn screening for CAH.

BACKGROUND: Newborn screening (NBS) reduces the risk of mortality in congenital adrenal hyperplasia (CAH), mainly due to the salt-wasting form of 21-hydroxylase deficiency. There is limited knowledge regarding the results of NBS in non-CAH primary adrenal insufficiency (non-CAH PAI). PATIENTS AND METHODS: Clinical and NBS for CAH data of neonates who were diagnosed with non-CAH PAI between January and December 2022 were examined. RESULTS: Patients (n = 6, 4 females) were presented with severe hyperpigmentation (n = 6), hypoglycemia (n = 4), hyponatremia (n = 3), hyperkalemia (n = 1), respiratory distress syndrome (n = 1) between 3rd hour to 2 months of life. All had normal NBS results. The median first-tier 17-hydroxyprogesterone (17OHP) concentration in NBS for CAH was 0.14 ng/mL (range; 0.05-0.85). Molecular studies revealed biallelic mutations in the MC2R (n = 4; 3 homozygous, 1 compound heterozygous), MRAP (n = 1) and STAR (n = 1) genes. Glucocorticoid with or without mineralocorticoid replacement was initiated once the diagnosis of non-CAH PAI was established. CONCLUSION: Neonates with non-CAH PAI have always normal NBS due to persistently low 17OHP, even when these newborn infants are severely symptomatic for adrenal insufficiency. Clinicians should be alert for signs of adrenal insufficiency in neonates, even if the patient has a 'normal' screening for CAH, so as not to delay diagnosis and treatment. This fact should be kept in mind particularly in countries where these conditions are more common than elsewhere.

Steroidogenic acute regulatory protein (STAR) deficiency: Our experience and systematic review for phenotype-genotype correlation.

OBJECTIVE: Lipoid congenital adrenal hyperplasia (LCAH) is caused by mutations in STAR. A systematic review of phenotype-genotype correlation and data on testicular histology in LCAH patients is unavailable. We aim to describe our experience and provide phenotype-genotype correlation. DESIGN, PATIENTS AND MEASUREMENTS: Retrospective review of three genetically proven LCAH patients from our centre and per-patient data analysis from a systematic review of 292 probands. The phenotypic subgroups of 46,XY were Group A (typical female genitalia), Group B (atypical genitalia) and Group C (typical male genitalia). RESULTS: We report three new LCAH probands from India, all diagnosed post-infancy with preserved gonadal function and one novel variant. The systematic review reports 46,XY to 46,XX LCAH ratio of 1.1 (155:140). Patients with 46,XY LCAH in Group A were diagnosed in infancy (116/117) and had higher mineralocorticoid involvement than Group C (96.4% vs. 75%, p = 0.035), whereas Group C had preserved gonadal function. Hyperplastic adrenals are noted in ~60% of LCAH diagnosed with primary adrenal insufficiency in infancy. There was no report of gonadal germ cell cancer and rare reports of germ cell neoplasia in situ in adolescents, especially with intraabdominal gonads. Two-thirds of LCAH probands were East-Asian and 11/16 regional recurrent variants were from East Asia. There was minimal overlap between variants in Groups A (n = 55), B (n = 9) and C (n = 8). All nonsense and frameshift and most of the splice-site variants and deletion/insertions were present in Group A. CONCLUSIONS: We report three new cases of LCAH from India. We propose a phenotype-derived genotypic classification of reported STAR variants in 46,XY LCAH.

DCE-MRI of the liver with sub-second temporal resolution using GRASP-Pro with navi-stack-of-stars sampling.

Respiratory motion-induced image blurring and artifacts can compromise image quality in dynamic contrast-enhanced MRI (DCE-MRI) of the liver. Despite remarkable advances in respiratory motion detection and compensation in past years, these techniques have not yet seen widespread clinical adoption. The accuracy of image-based motion detection can be especially compromised in the presence of contrast enhancement and/or in situations involving deep and/or irregular breathing patterns. This work proposes a framework that combines GRASP-Pro (Golden-angle RAdial Sparse Parallel MRI with imProved performance) MRI with a new radial sampling scheme called navi-stack-of-stars for free-breathing DCE-MRI of the liver without the need for explicit respiratory motion compensation. A prototype 3D golden-angle radial sequence with a navi-stack-of-stars sampling scheme that intermittently acquires a 2D navigator was implemented. Free-breathing DCE-MRI of the liver was conducted in 24 subjects at 3T including 17 volunteers and 7 patients. GRASP-Pro reconstruction was performed with a temporal resolution of 0.34-0.45 s per volume, whereas standard GRASP reconstruction was performed with a temporal resolution of 15 s per volume. Motion compensation was not performed in all image reconstruction tasks. Liver images in different contrast phases from both GRASP and GRASP-Pro reconstructions were visually scored by two experienced abdominal radiologists for comparison. The nonparametric paired two-tailed Wilcoxon signed-rank test was used to compare image quality scores, and the Cohen's kappa coefficient was calculated to evaluate the inter-reader agreement. GRASP-Pro MRI with sub-second temporal resolution consistently received significantly higher image quality scores (P < 0.05) than standard GRASP MRI throughout all contrast enhancement phases and across all assessment categories. There was a substantial inter-reader agreement for all assessment categories (ranging from 0.67 to 0.89). The proposed technique using GRASP-Pro reconstruction with navi-stack-of-stars sampling holds great promise for free-breathing DCE-MRI of the liver without respiratory motion compensation.

Implementing stereotactic arrhythmia radioablation with STOPSTORM.eu consortium support: intermediate results of a prospective Israeli single-institutional trial.

BACKGROUND: Ventricular tachycardia (VT) is a life-threatening arrhythmia originating from the heart's ventricles. Traditional treatments include antiarrhythmic medications, implantable cardioverter-defibrillators (ICDs), and catheter ablation. Stereotactic body radiation therapy (SBRT) targeting the arrhythmogenic focus in the left ventricle-stereotactic arrhythmia radioablation (STAR)-is an emerging treatment and may offer a potential solution for patients with refractory VT. OBJECTIVE: We designed an interventional prospective clinical trial in Israel aligned with the STOPSTORM.eu consortium's benchmarks, recommendations, and directives to assess the safety and efficacy of STAR in patients with refractory VT. METHODS: Our phase I/II single-institutional trial was approved by the Ministry of Health of Israel for 10 patients, initially assessing safety in the first 3 patients. We included patients with ICDs experiencing symptomatic monomorphic VT after an inadequate response to previous therapies. The primary endpoints were treatment-related serious adverse events and a reduction in VT burden as assessed by ICD interrogation. Secondary outcomes included a reduction in antiarrhythmic medications and changes in quality of life. RESULTS: From August 2023 to August 2024, 3 patients underwent STAR treatment. The prescription dose was a single fraction of 25 Gy. Planning target volumes were 47.8, 49.7, and 91.8 cc, and treatment was successfully delivered with no grade 3 or higher adverse events reported. Over a follow-up period of 12 months for the first patient and 8 months for the second one, no VT events were recorded after treatment. The third patient died from progressive heart failure 3 months after treatment. Left ventricular ejection fraction remained stable, and no significant radiation-induced inflammatory changes were noted. CONCLUSION: The initial results of this trial suggest that STAR can reduce VT episodes in patients with refractory VT without severe adverse effects. The study highlights the importance of international collaboration and standardization in pioneering new treatments. Further follow-up and additional patient data will be necessary to confirm these findings and evaluate long-term outcomes, including potential adjustments to antiarrhythmic medication regimens.