Kindai University

Purpose This study aimed to assess the potential of prognostic factors including consolidation tumor ratio (CTR) on treatment outcomes in patients with clinical stage 0–IA non‐small cell lung cancer (NSCLC) undergoing stereotactic body radiotherapy (SBRT). Methods The analysis included data of 63 patients with 67 lesions of clinical stage 0–IA NSCLC treated with SBRT. According to the Union for International Cancer Control 8th edition, the following tumor stages were observed: Tis, 3; T1mi, 2; T1a, 11; T1b, 29; and T1c, 22. The prescribed dose was 48 (range, 42–52) Gy in four fractions. Results The median follow‐up was 29.3 (range: 2.4–120.5) months. The five‐year local control (LC), overall survival, and progression‐free survival (PFS) rates were 89.4%, 60.3%, and 40.5%, respectively. Squamous cell carcinoma (Sq) and Dmax < 125 GyBED10 for planning target volume (PTV) were associated with a worse LC (p = 0.001 and 0.017, respectively). Patients with Sq, T1b–c, CTR > 0.25, PTV ≥ 30 cm³ tumors were associated with worse PFS than those with non‐Sq, ≤ cT1a, CTR ≤ 0.25, PTV < 30 cm³ tumors (p = 0.049, 0.004, 0.038, and 0.004, respectively). No recurrences, metastases, or deaths were found in patients with CTR ≤ 0.25 (n = 5). Conclusion In patients with stage 0–IA lung cancer treated with SBRT, tumors classified as ≤ T1a showed a better PFS than T1b–c. NSCLC with a low CTR of ≤ 0.25 seemed to have a low risk of recurrence after SBRT.

Purpose The aim of this study was to investigate the prognostic impact of thoracic extra-regional lymph node metastasis (M1b-LYM, determined by the 12th edition of the Japanese Classification of Esophageal Cancer) in definitive radiotherapy for esophageal squamous cell carcinoma. Methods Eighty-six consecutive patients who underwent definitive radiotherapy for esophageal squamous cell carcinoma between 2017 and 2022 at our institute were included in this retrospective study. Progression-free survival (PFS), overall survival (OS), distant metastasis (DM), and loco-regional recurrence (LR) were compared between patients with and without M1b-LYM using Kaplan–Meier or cumulative incidence function analysis. Results Among the 86 patients, 15 had M1b-LYM metastasis (the M1b( +) group) and 71 had no M1b-LYM metastasis (the M1b(-) group). The median follow-up period was 38 months. The 2-year PFS, OS, cumulative incidence of DM, and cumulative incidence of LR for the M1b(-) group versus M1b( +) group were 41% vs 20% (p = 0.129), 58% vs 47% (p = 0.172), 31% vs 33% (p = 0.906), and 31% vs 60% (p = 0.0369), respectively. Multivariate analysis showed that M1b( +) was associated with higher LR (p = 0.0350), T stage was associated with poorer PFS (p = 0.0138), and omitting chemotherapy was associated with poorer PFS (p = 0.0160) and OS (p < 0.01). Conclusion The presence of thoracic extra-regional lymph node metastasis was associated with poor loco-regional control but not distant metastasis or survival in esophageal squamous cell carcinoma patients after definitive radiotherapy. Trial registration number This study was retrospectively registered on 21 June 2024 (R06-053).

Two pairs of chiral perylene-based luminescent materials, namely ( R,R )/ (S,S )-N,N’-bis(1-phenylethyl)perylene-3,4,9,10-tetracarboxylic diimide [( R,R )/( S,S )- BPP ] and ( R,R )/( S,S )-N,N’-bis(1-cyclohexylethyl)perylene-3,4,9,10-tetracarboxylic diimide [( R,R )/( S,S )- CPDI ], were doped into a nematic liquid crystal with a low phase transition temperature, 4'-hexyl-4-biphenylcarbonitrile. The...

Saintpaulia (African violet) pigmentation is notoriously unstable and sometimes forms white stripes, particularly following passage through tissue culture. White‐striped petals were thought to be due to periclinal chimeras, but we confirmed that white stripes result from epigenetic regulation rather than periclinal chimeras based on the flower color traits of plants obtained from tissue culture. Gene expression in several plant lines, anthocyanin quantification, bisulfite sequencing, and methylation analyses were used to demonstrate the presence of a single MYB gene responsible for pigment variation. We identified SiMYB2 as the cause of variations in tissue color patterning, and that two RNAs were generated from SiMYB2. SiMYB2‐Long was expressed in colored tissues, while SiMYB2‐Short was expressed only in noncolored tissues. Functional analyses revealed that SiMYB2‐Long is an anthocyanin biosynthesis activator and SiMYB2‐Short is nonfunctional. Exon 3 of SiMYB2 was generated by the insertion of a transposon‐like sequence. A mutant lacking the element was obtained from cultivars with noncolored tissues. Anthocyanin content and SiMYB2‐Long expression in the mutant were greatly increased compared to wild‐type. Our results suggest that the white‐striped petals of Saintpaulia are not formed by periclinal chimeras but through the transcriptional selectivity of epigenetically regulated SiMYB2.

OBJECTIVE This study aimed to investigate the progression of β-cell dysfunction and its predictors in Japanese patients with type 1 diabetes, using data from the nationwide, multicenter, prospective longitudinal Japanese Type 1 Diabetes Database Study (TIDE-J). RESEARCH DESIGN AND METHODS TIDE-J enrolled 314 Japanese individuals with type 1 diabetes, including 165 with acute-onset, 105 with slowly progressive, and 44 with fulminant type 1 diabetes. Clinical data, including C-peptide levels, glycemic control, and autoantibody status, were collected annually for up to 14 years. HLA genotypes were analyzed at study entry. The time to insulin depletion was analyzed using survival curves and Cox proportional hazards models to determine predictive factors. RESULTS The rate of undetectable C-peptide varied significantly among subtypes. At 5 years after onset, 43.1% (n = 55) of patients with acute-onset, 9.1% (n = 7) with slowly progressive, and 93.2% (n = 38) with fulminant type 1 diabetes reached undetectable C-peptide. Even within acute-onset type 1 diabetes, a marked interindividual variation was observed in the progression toward β-cell depletion. HLA genotypes influenced progression rates as follows: DRB1*04:05-DQB1*04:01/DRB1*04:05-DQB1*04:01 (DR4/DR4) carriers exhibited slower β-cell depletion, whereas DR4/DRB1*08:02-DQB1*03:02 (i.e., DR4/DR8) and DR4/DRB1*09:01-DQB1*03:03 (i.e., DR4/DR9) were associated with a rapid progression. For slowly progressive type 1 diabetes, low BMI, GAD antibody positivity, and absence of the DRB1*15:01-DQB1*06:02 or DRB1*15:02-DQB1*06:01 (i.e., DR2) haplotype were predictive of progression to insulin dependence. CONCLUSIONS This study elucidates the heterogeneity in β-cell dysfunction among Japanese individuals with type 1 diabetes and identifies genetic and clinical predictors of disease progression. These findings provide insights for individualized management strategies and future therapeutic interventions.

Objective This study investigated the association between smoking and myasthenia gravis (MG), a chronic autoimmune disorder that affects neuromuscular junctions. Methods Data were collected from the Japan MG Registry 2021 survey conducted between April and October 2021. MG severity was assessed using the MG activities of daily living and MG Foundation of America (MGFA) scores, which were calculated as the number of cigarettes smoked per day multiplied by the number of years smoked. We compared the smoking rates of individuals with and without MG stratified by age and sex. Results Of the 1,407 patients selected from the Japanese registry, higher smoking rates were observed in patients with MG than in the general population. Compared with never-smokers, women with MG who smoked were younger and had a higher prevalence of ocular symptoms. A weak correlation was observed between MGFA and Brinkman indices among men with MG who smoked. No correlation was observed between smoking status and MG severity in women who smoked. Conclusion This study utilized one of the largest datasets on MG and smoking; thus, it provides valuable insights into the association between smoking and MG.

In this study, we reveal a novel relationship between RNF213, an E3 ubiquitin ligase associated with Moyamoya disease (MMD) and the ubiquitination of both endogenous and pathogenic substrates, and EGFR, the epithelial growth factor receptor involved in cell growth, angiogenesis, and cancer. RNF213 knockdown or knockout in HeLa and A549 cells markedly reduces EGFR phosphorylation at key tyrosine sites following EGF and TGFα stimulation. In RNF213 knockout cells, HER2 phosphorylation, typically activated through heterodimerization with EGFR, and Src recruitment and/or phosphorylation are also diminished. Mutations in the RNF213 RING, RZ finger, or AAA+ domains, including the prevalent R4810K mutation in MMD, consistently reduce EGFR phosphorylation. In vivo, EGF injections increase EGFR and HER2 phosphorylation in WT but not in RNF213 knockout mice. Despite the reduced phosphorylation levels of these tyrosine kinases in knockout cells, the activation of downstream signals such as AKT, ERK1/2, and STAT3 remains unaffected, although phosphorylation of PLCγ, a key mediator of Ca²⁺ release, is selectively reduced by RNF213 knockout. These findings demonstrate that RNF213 modulates EGFR‐related pathways and specific downstream signal pathways, possibly affecting physiologic and pathogenic angiogenesis, and may have implications for unraveling the etiology of MMD and for developing cancer therapies that target RNF213.

During neuronal differentiation, gene transcription patterns change in response to both intrinsic and extrinsic cues. Chromatin regulation at regulatory elements plays a key role in this process. However, how chromatin accessibility evolves in vivo in cortical neurons remains unclear. Here, we established a method for labeling differentiating neurons with specific birthdates. Using this method, we traced the four-day differentiation process of in vivo deep-layer excitatory neurons in the mouse embryonic cortex and examined changes in the genome-wide transcription pattern and chromatin accessibility using RNA-sequencing and DNase-sequencing, respectively. We found that genomic regions of genes linked to mature neuronal functions, including deep-layer-specific and stimulus-responsive genes, became accessible even at the embryonic stage. Additionally, our results indicated the involvement of bivalent marks in neural precursor/stem cells and Dmrt3 and Dmrta2 in regulating chromatin accessibility during neuronal differentiation. These findings highlight the importance of chromatin regulation in embryonic neurons, enabling the timely activation of neuronal genes during maturation.

Global studies consistently highlight a direct relationship between habitat and species losses, and human population and economic growth. Nevertheless, countries are experiencing below-replacement human fertility and starting to depopulate; among these countries, Japan is a global forerunner. To better understand whether human depopulation automatically yields environmentally restorative outcomes, we examine the impacts of human depopulation on aspects of biodiversity in Japan. Alongside population, land use and surface temperature, we analyse biodiversity change among 464 taxonomic species of bird, butterfly, firefly and frog egg masses, and 2,922 native and non-native plant species in wooded, agricultural and peri-urban landscapes across Japan over periods of 5–17 years from 2004. Irrespective of human population increase or decrease, biodiversity losses continue among most species studied mainly because of change in agricultural land use, either due to urbanization, disuse and abandonment, or intensification. Only where human numbers are currently stable, biodiversity is also more stable, although we anticipate that this may also change as ageing deepens into depopulation in these areas. We conclude by urging countries facing depopulation to account for its outcomes in their biodiversity conservation and restoration strategies.

We found repetitive splitting and reaggregation of particle clouds falling in a dilute surfactant solution with viscoelastic properties. To investigate this sedimentation behavior, we conducted two-dimensionally constrained experiments. The behavior is observed around the particle clouds at the tip of particle-rich streaks and sustained by the negative wake. The negative wake generated behind the particle clouds plays two key roles in the mechanism of the splitting and reaggregation of the clouds: it decelerates the preceding clouds and increases the local apparent density of the particle suspension phase. The latter effect is due to the particle accumulation surrounding the negative wake. Because of this local increase in the apparent density, subsequent particle clouds are generated and can catch up with the decelerated preceding ones, forming a new particle cloud showing the repetitive splitting and reaggregation.