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We aimed to evaluate the radiographic and clinical outcomes after gamma knife radiosurgery (GKRS) for trigeminal schwannomas (TSs). A total of 87 patients who underwent GKRS for TSs between 1990 and 2020 were enrolled. The mean tumor volume was 4.3 cm 3 . The median prescribed dose for the margins of the tumor was 13 Gy. The median follow-up duration was 64.3 months (range 12.0–311.5 months). The overall local tumor control rate was 90%, and the symptom response rate was 93%. The response rate for each symptom was 88% for facial pain, 97% for facial sensory change, and 86% for cranial nerve deficits. Nineteen (22%) patients showed transient swelling, which had regressed at the time of the last follow-up. Cystic tumors were associated with transient swelling ( p  = 0.04). A tumor volume of < 2.7 cm 3 was associated with local tumor control in univariable analysis. Transient swelling was associated with symptom control failure in both univariable and multivariable analyses ( p  = 0.04, odds ratio 14.538). GKRS is an effective treatment for TSs, both for local control and symptom control.

This study evaluates a novel three-dimensional (3D) quality assurance (QA) device, the Mobile Phosphor Probe (MPP), for pretreatment dose verification in Gamma Knife (GK) stereotactic radiosurgery. The MPP system consists of a cylindrical phantom with a phosphor screen, an imaging unit with a charge-coupled device (CCD) camera, and a motorized driving unit. Dose distributions are reconstructed from images using a lookup table, which correlates CCD pixel optical density with dose values, calibrated against EBT3 film readings. Results show that the full width at half maximum of normalized dose distributions between film and CCD were consistent within a 0.2 mm margin. A 3D dose distribution was constructed by stacking two-dimensional images obtained at 0.3 mm intervals over a ± 30 mm range in the superior-inferior direction. Validation was achieved by comparing the reconstructed 3D doses with planned distributions across multiple planes using gamma evaluation. All cases within the 20–80% isodose line (IDL) range achieved a 95% gamma passing rate under 2.0%/2.0 mm criteria, and the 1.0%/1.0 mm criteria were met at the 50% IDL in all dimensions. The MPP system demonstrates potential as an efficient patient-specific QA tool for GK radiosurgery, offering a streamlined alternative to traditional film dosimetry.

The strength of the T cell receptor interaction with self-ligands affects antigen-specific immune responses. However, the precise function and underlying mechanisms are unclear. Here, we demonstrate that naive CD8 + T cells with relatively high self-reactivity are phenotypically heterogeneous owing to varied responses to type I interferon, resulting in three distinct subsets, CD5 lo Ly6C – , CD5 hi Ly6C – , and CD5 hi Ly6C + cells. CD5 hi Ly6C + cells differ from CD5 lo Ly6C – and CD5 hi Ly6C – cells in terms of gene expression profiles and functional properties. Moreover, CD5 hi Ly6C + cells demonstrate more extensive antigen-specific expansion upon viral infection, with enhanced differentiation into terminal effector cells and reduced memory cell generation. Such features of CD5 hi Ly6C + cells are imprinted in a steady-state and type I interferon dependence is observed even for monoclonal CD8 + T cell populations. These findings demonstrate that self-reactivity controls the functional diversity of naive CD8 + T cells by co-opting tonic type I interferon signaling. There is heterogeneity in the response to self-ligands within the naïve CD8 + T cell pool and the consequences of this are unclear. Here the authors show subsets of naïve CD8 + T cells which differ in expression of Ly6C and CD5 and response to viral infection through regulation by type I IFN signalling.

Polycystic ovary syndrome (PCOS) is a common disease that has an effect on approximately 10% of women of childbearing age. Although there is evidence regarding the role of lifestyle factors in the development of PCOS, the exact etiology remains unclear. Additionally, metformin is used in the treatment of PCOS but its role remains unclear. We compared the effects of lifestyle modification (LSM) + metformin and metformin alone on PCOS. We performed a systematic review by searching electronic databases for publications until December 2019. The primary endpoints were clinical outcomes, such as menstrual cycles and pregnancy rates, and the secondary endpoints were anthropometric, metabolic, and androgenic parameters. The meta-analysis revealed that there was no significant difference in the improvements in the menstrual cycles between LSM and metformin alone (weighted mean difference [MD] = 1.62) and between LSM + metformin and LSM (MD = 1.20). The pregnancy rates and body mass indices were not significantly different between LSM and metformin alone (MD = 1.44 and −0.11, respectively). LSM reduced insulin resistance (MD = −0.52) and increased serum levels of sex hormone-binding globulins (MD = 8.27) compared with metformin. Therefore, we suggest recommending lifestyle modifications actively to women with PCOS if they do not have indications for metformin.

The role of brain somatic mutations in Alzheimer’s disease (AD) is not well understood. Here, we perform deep whole-exome sequencing (average read depth 584×) in 111 postmortem hippocampal formation and matched blood samples from 52 patients with AD and 11 individuals not affected by AD. The number of somatic single nucleotide variations (SNVs) in AD brain specimens increases significantly with aging, and the rate of mutation accumulation in the brain is 4.8-fold slower than that in AD blood. The putatively pathogenic brain somatic mutations identified in 26.9% (14 of 52) of AD individuals are enriched in PI3K-AKT, MAPK, and AMPK pathway genes known to contribute to hyperphosphorylation of tau. We show that a pathogenic brain somatic mutation in PIN1 leads to a loss-of-function mutation. In vitro mimicking of haploinsufficiency of PIN1 aberrantly increases tau phosphorylation and aggregation. This study provides new insights into the genetic architecture underlying the pathogenesis of AD. The role of brain somatic mutations in neurodegenerative diseases such as Alzheimer’s disease (AD) is not well understood. Here the authors carry out high-depth exome sequencing ~500× on brain tissue from patients with AD and controls, and identify mutations in a number of genes that are known to contribute to phosphorylation and aggregation of tau, including PIN1.

Summary Panax ginseng C. A. Meyer, reputed as the king of medicinal herbs, has slow growth, long generation time, low seed production and complicated genome structure that hamper its study. Here, we unveil the genomic architecture of tetraploid P. ginseng by de novo genome assembly, representing 2.98 Gbp with 59 352 annotated genes. Resequencing data indicated that diploid Panax species diverged in association with global warming in Southern Asia, and two North American species evolved via two intercontinental migrations. Two whole genome duplications (WGD) occurred in the family Araliaceae (including Panax) after divergence with the Apiaceae, the more recent one contributing to the ability of P. ginseng to overwinter, enabling it to spread broadly through the Northern Hemisphere. Functional and evolutionary analyses suggest that production of pharmacologically important dammarane‐type ginsenosides originated in Panax and are produced largely in shoot tissues and transported to roots; that newly evolved P. ginseng fatty acid desaturases increase freezing tolerance; and that unprecedented retention of chlorophyll a/b binding protein genes enables efficient photosynthesis under low light. A genome‐scale metabolic network provides a holistic view of Panax ginsenoside biosynthesis. This study provides valuable resources for improving medicinal values of ginseng either through genomics‐assisted breeding or metabolic engineering.

Watson for Oncology (WfO) is a clinical decision support system driven by artificial intelligence. In Korea, WfO is used by multidisciplinary teams (MDTs) caring for cancer patients. This study aimed to investigate the effect of WfO use on hospital satisfaction and perception among patients cared for by MDTs. This was a descriptive study that used a written survey to gather information from cancer patients at a hospital in Korea. The rate of positive change in patient perception after treatment was 86.8% in the MDT-WfO group and 71.2% in the MDT group. In terms of easily understandable explanations, the MDT-WfO (9.53 points) group reported higher satisfaction than the MDT group (9.24 points). Younger patients in the MDT-WfO group showed high levels of satisfaction and reliability of treatment. When WfO was used, the probability of positive change in patient perception of the hospital was 2.53 times higher than when WfO was not used. With a one-point increase in overall satisfaction, the probability of positive change in patient perception of the hospital increased 1.97 times. Therefore, if WfO is used appropriately in the medical field, it may enhance patient satisfaction and change patient perception positively.

Hybridizing two known antimicrobial peptides (AMPs) is a simple and effective strategy for designing antimicrobial agents with enhanced cell selectivity against bacterial cells. Here, we generated a hybrid peptide Lf-KR in which LfcinB6 and KR-12-a4 were linked with a Pro hinge to obtain a novel AMP with potent antimicrobial, anti-inflammatory, and anti-biofilm activities. Lf-KR exerted superior cell selectivity for bacterial cells over sheep red blood cells. Lf-KR showed broad-spectrum antimicrobial activities (MIC: 4–8 μM) against tested 12 bacterial strains and retained its antimicrobial activity in the presence of salts at physiological concentrations. Membrane depolarization and dye leakage assays showed that the enhanced antimicrobial activity of Lf-KR was due to increased permeabilization and depolarization of microbial membranes. Lf-KR significantly inhibited the expression and production of pro-inflammatory cytokines (nitric oxide and tumor necrosis factor‐α) in LPS-stimulated mouse macrophage RAW264.7 cells. In addition, Lf-KR showed a powerful eradication effect on preformed multidrug-resistant Pseudomonas aeruginosa (MDRPA) biofilms. We confirmed using confocal laser scanning microscopy that a large portion of the preformed MDRPA biofilm structure was perturbed by the addition of Lf-KR. Collectively, our results suggest that Lf-KR can be an antimicrobial, anti-inflammatory, and anti-biofilm candidate as a pharmaceutical agent.

Background Knee osteoarthritis (OA) is a leading cause of disability, with current treatment options often falling short of providing satisfactory outcomes. Autologous-cultured adipose-derived mesenchymal stem cells (ADMSCs) and stromal vascular fractions (SVFs) have emerged as potential regenerative therapies. Methods A comprehensive search was conducted among multiple databases for studies up to June 2023. The risk of bias was assessed in randomized and non-randomized studies, adhering to PRISMA guidelines. The study has been registered with PROSPERO (CRD 42023433160). Results Our analysis encompassed 31 studies involving 1,406 patients, of which, 19 studies with 958 patients were included in a meta-analysis, examining both SVF and autologous-cultured ADMSC methods. Significant pain reduction was observed with autologous-cultured ADMSCs starting at 3 months (MD = −2.43, 95% CI, −3.99, −0.86), whereas significant pain mitigation in response to SVF therapy was found to start at 12 months (MD = −2.13, 95% CI, −3.06, −1.21). Both autologous-cultured ADMSCs and SVF provided significant improvement in knee function starting at 12 months (MD = −9.19, 95% CI, −12.48, −5.90 vs. MD = −9.09, 95% CI, −12.67, −5.51, respectively). We found no evidence of severe adverse events linked directly to ADMSC therapy. Conclusion Autologous-cultured ADMSCs offer a promising alternative for more rapid pain relief in knee OA, with both ADMSCs and SVF demonstrating substantial long-term benefits in joint function and cartilage regeneration, in the absence of any severe ADMSC-related adverse events.

Improving early cancer detection has the potential to substantially reduce cancer-related mortality. Cell-free methylated DNA immunoprecipitation and high-throughput sequencing (cfMeDIP–seq) is a highly sensitive assay capable of detecting early-stage tumors. We report accurate classification of patients across all stages of renal cell carcinoma (RCC) in plasma (area under the receiver operating characteristic (AUROC) curve of 0.99) and demonstrate the validity of this assay to identify patients with RCC using urine cell-free DNA (cfDNA; AUROC of 0.86). A cell-free DNA-methylation sequencing assay accurately identifies renal cell carcinoma using plasma and urine samples.