SRRM2 encodes a nuclear protein, with functions in pre-mRNA splicing and the formation of nuclear speckles via liquid-liquid phase separation. Despite its critical role in cellular function, the association between SRRM2 and neurodevelopmental disorders is not well-understood. In this study, we reported a case of a patient exhibiting developmental delay, intellectual disability, delayed language development, facial dysmorphism, macrocephaly, short hands and feet, hyperphagia, and hypotonia, which are similar to the characteristics of previously reported cases of SRRM2-associated neurodevelopmental disorders. Notably, the patient became overweight and subsequently developed several obesity-related complications due to uncontrolled hyperphagia. Employing whole exome sequencing (WES) and Sanger sequencing, we identified a novel missense mutation in SRRM2 (NM_016333: c.4661A > T, p.Q1554L). This mutation is classified as “Likely Pathogenic” based on the American College of Medical Genetics and Genomics (ACMG) guideline. Overall, this study contributes to the expanding spectrum of known mutations in SRRM2, enhances our understanding of its clinical implications, and offers crucial data for the diagnosis and management of affected individuals.

• Book : ()
• Pub. Date : 2025
• Page :
• Keyword :

AbstractPurposeThis work describes a single institution experience of commissioning a real‐time target tracking and beam control system, known as comprehensive motion management, for a 1.5 T Elekta MR‐Linac.MethodsAnatomical tracking and radiation beam control were tested using the MRI4D Quasar motion phantom. Multiple respiratory breathing traces were modeled across a range of realistic regular and irregular breathing patterns ranging between 10 and 18 breaths per minute. Each of the breathing traces was used to characterize the anatomical position monitoring (APM) accuracy, and beam latency, and to quantify the dosimetric impact of both parameters during a respiratory‐gated delivery using EBT3 film dosimetry. Additional commissioning tasks were performed to verify the dosimetric constancy during beam gating and to expand our existing quality assurance program.ResultsIt was determined that APM correctly predicted the 3D position of a dynamically moving tracking target to within 1.5 mm for 95% of the imaging frames with no deviation exceeding 2 mm. Among the breathing traces investigated, the mean latency ranged between −21.7 and 7.9 ms with 95% of all observed latencies within 188.3 ms. No discernable differences were observed in the relative profiles or cumulative output for a gated beam relative to an ungated beam with minimal dosimetric impact observed due to system latency. Measured dose profiles for all gated scenarios retained a gamma pass rate of 97% or higher for a 3%/2 mm criteria relative to a theoretical gated dose profile without latency or tracking inaccuracies.ConclusionMRI‐guided target tracking and automated beam delivery control were successfully commissioned for the Elekta Unity MR‐Linac. These gating features were shown to be highly accurate with an effectively small beam latency for a range of regular and irregular respiratory breathing traces.

• Book : ()
• Pub. Date : 2025
• Page :
• Keyword :

Aim. To study of oxidative processes in testicular tissues after gamma irradiation. Material and methods. Using the polarographic method, the rate of oxygen absorption on endogenous and exogenous substrates (Vend, Vsuc, Vglu, Vdnf) and with specific inhibitors of tissue respiration of amytal and sodium malonate (Vam, Vmal) in testicular tissues at different times (3, 10, 40 days) after total single gamma irradiation (1.0 Gr). Results. It was found that, in the testicular tissues of rats at different times (3rd, 10th, 40th day) after total single gamma irradiation (1.0 Gy). In the early period (72 hours) after irradiation, (Vend) decreased by 14.7 % (p < 0.05), (Vsuc) by 18.6 % (p < 0.05) and (Vglu) by 10.9 % (p < 0.05) compared with the control. After 10 days, on the contrary, there was an increase in (Vend) by 108.2 % (p < 0.05), in the presence of exogenous succinate and glutamate substrates, increased (Vsuc) by 45.1 % (p < 0.05) and (Vglu) by 112 % (p < 0.05), SDdnf decreased by 12.8 % (p < 0.05), and with inhibitors, low-resistance respiration (MRD) increased by 9.4 % (p < 0.05). On day 40 (Vend, Vsuc, Vglu) increased by 120.7 % (p < 0.05), 124.8 % (p < 0.05) and 97.1 % (p < 0.05), respectively, SDdnf decreased by 11.5 % (p < 0.001), amytal resistant respiration (ARD) by 30.6 % (p < 0.05) and MRD by 11.7 % (p < 0.05). Conclusion. Increased oxygen uptake was accompanied by a significant decrease in SDdnf in both experimental groups (10th and 40th days), which suggested the threat of disconnection of oxidation and phosphorylation processes. A decrease in MPD also indicates a decrease in the contribution of fatty acids (FA) to the energy supply of testicular tissue.

• Book : 14(6)
• Pub. Date : 2025
• Page : pp.17-23
• Keyword :

Abstract Background Accurately predicting the malignant risk of ground-glass nodules (GGOs) is crucial for precise treatment planning. This study aims to utilize convolutional neural networks based on dual-time-point 18F-FDG PET/CT to predict the malignant risk of GGOs. Methods Retrospectively analyzing 311 patients with 397 GGOs, this study identified 118 low-risk GGOs and 279 high-risk GGOs through pathology and follow-up according to the new WHO classification. The dataset was randomly divided into a training set comprising 239 patients (318 lesions) and a testing set comprising 72 patients (79 lesions), we employed a self-configuring 3D nnU-net convolutional neural network with majority voting method to segment GGOs and predict malignant risk of GGOs. Three independent segmentation prediction models were developed based on thin-section lung CT, early-phase 18F-FDG PET/CT, and dual-time-point 18F-FDG PET/CT, respectively. Simultaneously, the results of the dual-time-point 18F-FDG PET/CT model on the testing set were compared with the diagnostic of nuclear medicine physicians. Results The dual-time-point 18F-FDG PET/CT model achieving a Dice coefficient of 0.84 ± 0.02 for GGOs segmentation and demonstrating high accuracy (84.81%), specificity (84.62%), sensitivity (84.91%), and AUC (0.85) in predicting malignant risk. The accuracy of the thin-section CT model is 73.42%, and the accuracy of the early-phase 18F-FDG PET/CT model is 78.48%, both of which are lower than the accuracy of the dual-time-point 18F-FDG PET/CT model. The diagnostic accuracy for resident, junior and expert physicians were 67.09%, 74.68%, and 78.48%, respectively. The accuracy (84.81%) of the dual-time-point 18F-FDG PET/CT model was significantly higher than that of nuclear medicine physicians. Conclusions Based on dual-time-point 18F-FDG PET/CT images, the 3D nnU-net with a majority voting method, demonstrates excellent performance in predicting the malignant risk of GGOs. This methodology serves as a valuable adjunct for physicians in the risk prediction and assessment of GGOs.

• Book : 25(1)
• Pub. Date : 2025
• Page :
• Keyword :

• Book : ()
• Pub. Date : 2025
• Page : pp.1-1
• Keyword :

• Book : ()
• Pub. Date : 2025
• Page :
• Keyword :

The gut microbiome can be shaped by both intrinsic host factors and extrinsic environmental factors. However, the relative importance of intrinsic and extrinsic factors in gut microbial composition has rarely been investigated, particularly for a single host across its natural range. Here, we characterise the gut microbiome of an endemic, endangered antelope, the blackbuck or Antilope cervicapra. We evaluated the influence of seven predictor variables, which were classified into intrinsic and extrinsic factors, on the gut microbiome. The intrinsic factors are nucleotide diversity (mitochondrial and nuclear) and blackbuck population density, whereas extrinsic factors are temperature, precipitation, distance to human settlement and anthropogenic land‐use. We determined which of these seven variables explains greater variation in the microbiome within (α‐diversity) and between (β‐diversity) the blackbuck hosts. We analysed the microbiome of n = 60 blackbuck hosts from ten different populations across India. We recorded 11 800 unique OTUs across 30 known phyla and 2.9 million reads. We find an average of 2056 OTUs per individual, with Bacillota and Bacteroidota being the most dominant phyla. Overall, we also show that the genetic diversity (intrinsic) of the host is more important than their environment (extrinsic) for both within‐ and between‐host variation in the microbiome of blackbuck. Our results suggest that an increase in genetic relatedness between blackbuck hosts can lead to a decrease in the variation of their gut microbial composition. Therefore, conservation efforts should be directed to not only preserve natural habitats but also increase the genetic pool of the blackbuck populations, which will positively impact their survival through diverse gut microbiomes.

• Book : ()
• Pub. Date : 2025
• Page :
• Keyword :

• Book : ()
• Pub. Date : 2025
• Page :
• Keyword :

AbstractThe magnitude of Type I interferon (IFN) mediated innate immune response within the tumor microenvironment (TME) critically influences the effectiveness of radiotherapy. Unfortunately, due to a myriad of resistance mechanisms, the double‐stranded DNA (dsDNA) signals produced by tumor cells postradiotherapy often induce a diminished response from immune cells. Through chemical screening targeting deubiquitinating enzymes, we identified USP1 (Ubiquitin Specific Peptidase 1) inhibitor as an enhancer of post‐radiotherapy dsDNA responses. Mechanistically, within the context of immune‐stimulatory cells in TME, USP1 serves as a suppressor in the stress‐mediated stages of the cGAS (Cyclic GMP‐AMP synthase) ‐STING (Stimulator of interferon genes protein) signaling pathway, specifically affecting the trafficking of STING from endoplasmic reticulum to Golgi apparatus. It is elucidated that SAR1A (Secretion associated Ras related GTPase 1A) requires K27‐linked oligo‐ubiquitination to assemble the STING‐COP‐II (Coat protein II) transport complex for STING trafficking. USP1 counteracts this activation by removing SAR1A ubiquitination, thereby blocking STING trafficking and activation. Consequently, pharmacological USP1 inhibition using ML323 sustains SAR1A ubiquitination and COP‐II complex formation, significantly enhancing STING trafficking and subsequent Type I IFN production. This intervention substantially amplifies radiotherapy‐induced immune activation in the TME, providing a strategic approach to overcome therapeutic resistance and synergize radiotherapy with immunotherapies.

• Book : ()
• Pub. Date : 2025
• Page :
• Keyword :

AbstractAqueous metal‐selenium batteries based on chalcogenide cathodes, despite their multi‐electron conversion‐type redox reactions and rapid kinetics, suffer from short lifespans and unclear capacity degradation mechanisms. The interfacial interactions between doped carbon and chalcogenides correlate closely with the electrochemical structural evolution. Hence, flower‐like Cu2−xSe wrapped with ultrathin N‐doped carbon layer (Cu2−xSe@N‐C) is synthesized via a simple γ radiation‐pyrolysis route for the first time. The Cu2−xSe@N‐C cathode displays a high‐rate performance and long‐term stability, with a respective capacity of 310.6 mAh g−1 at 20 A g−1 and a capacity retention rate of 92.9% after 30 000 cycles over 2000 h at 5 A g−1. Ex situ X‐ray diffraction and X‐ray photoelectron spectroscopy confirm the reversible Cu storage mechanism of the Cu2−xSe@N‐C cathode and the issues of volume expansion and oxidative dissolution related to the capacity degradation of the Cu2−xSe cathode. Furthermore, X‐ray absorption analysis and theoretical calculations reveal the presence of Se─C interactions between the ultrathin N‐doped carbon and Cu2−xSe. As a result, the physical and chemical dual‐protection of N‐doped carbon via Se‐C not only effectively stabilizes the structural evolution of Cu2−xSe but also endows it with faster electrode reaction kinetics.

• Book : ()
• Pub. Date : 2025
• Page :
• Keyword :