Search Results (109)

Treatment-associated regression of tumors outside the irradiated field has occasionally been reported, but the underlying mechanisms remain unclear, particularly in the context of central nervous system (CNS)–directed therapy. Glioblastoma (GBM) is commonly treated with radiotherapy and temozolomide, both of which may influence tumor biology and the systemic environment. We report a patient with synchronous primary GBM and early-stage lung adenocarcinoma who underwent craniotomy followed by intensity-modulated radiotherapy with concurrent temozolomide for GBM. During GBM-directed chemoradiotherapy, the untreated pulmonary lesion demonstrated progressive regression without any lung-specific therapy, temporally coinciding with CNS-targeted treatment. Although comprehensive immunophenotyping was not feasible, longitudinal changes in the proportion of peripheral blood lymphocytes were observed during therapy. These findings represent a clinical observation characterized by a temporal association between CNS-directed treatment and regression of a distant, non-irradiated tumor. However, the underlying mechanism remains uncertain, and a contribution from systemic temozolomide exposure cannot be excluded. While treatment-related systemic effects may be considered, no specific causal mechanism can be established based on this single case. This case highlights an unusual clinical observation that may warrant further investigation. Further studies are needed to clarify the relationship between CNS-directed therapies and systemic tumor behavior. Full article

Background: Accurate dietary assessment is vital for preventing malnutrition in aging populations, particularly in home-care settings. Although Large Multimodal Models (LMMs) for nutrient estimation are evolving, their nutrient-specific accuracy requires rigorous validation. Methods: Fifteen standardized hospital meals were photographed under controlled conditions (90-degree angle, 500 lux). Ground truth values were determined by direct weighing. Estimates for energy and macronutrients were performed by 10 registered dietitians (RDs) and 10 AI models (including ChatGPT-4o and Gemini 1.5 Pro). Accuracy was assessed using Pearson’s correlation, Mean Absolute Error (MAE), and Bland–Altman analysis to quantify systematic bias. Results: For energy and carbohydrates, RDs and top-performing AI models (notably ChatGPT-4o and Gemini 1.5 Pro) demonstrated practical accuracy (r > 0.8, frequently within ±10% range). However, accuracy for protein and lipids was significantly lower across all AI models. Specifically, all AI models exhibited a substantial systematic overestimation of lipids (Mean Bias > +20%, p < 0.01), highlighting a critical “invisible nutrient” bias. Conclusions: Current AI tools show potential for caloric and carbohydrate monitoring but struggle with lipid and protein density. These findings emphasize the need for human–AI collaboration (“human-in-the-loop”) and the integration of cooking metadata to improve clinical utility in geriatric nutrition. Full article

Using factual information on background knowledge, costs, personnel numbers, resources, and facilities from the Manhattan Project, we examine the feasibility of the development of nuclear weapons in Germany in World War II. We conclude that, while for various reasons, a uranium bomb would have been technically and economically out of reach in Germany, a few plutonium bombs might have been possible had a coordinated aggressive project been initiated no later than about mid-1940. However, the German scientists involved never established an understanding of the functioning of an atomic bomb as contained in the Frisch–Peierls memorandum and were never asked to provide such a basis on which a decision on an atomic bomb program could be based. This means that a German atomic bomb program did not fail as is often assumed; rather, it was never started. The German uranium project was never more than a scientific mission to study the possibilities offered by the newly discovered source of nuclear power. Full article

Ice cores retrieved from the Third Pole provide invaluable information about past and present environmental changes. Here we present, for the first time, a continuous tritium and plutonium isotope profile of the Puruogangri ice field, Tibetan Plateau, China, for the last 70 years. The age-depth profile has been composed by different time anchors such as the onset of thermonuclear weapon tests, the so-called bomb peak of tritium, the Chernobyl event, and the time of ice coring. The accumulation rate of ice calculated from the age-depth relation shows a decrease after 1963. It was 57, 15, and 22 cm/year in the periods of 1954–1963, 1963–1986, and 1986–2023, respectively. The concentrations of plutonium isotopes (²³⁹Pu: up to 2.7 fg/g) are slightly lower than those of the Belukha ice core, Siberian Altai, Russia, and almost the same as the Miaoergou glacier, eastern Tien Shan, China. Contrary to this latter ice core profile, the Puruogangri plutonium profile reflects that the Chinese weapon test started in 1966. This is confirmed by the tritium time series as well. ²⁴⁰Pu/²³⁹Pu atomic ratios vary between 0.14 and 0.23, with an average of 0.177 ± 0.024. The overall obtained local fallout of ²³⁹Pu and ²⁴⁰Pu is 13.2 and 9.0 Bq/m² (4.0 and 1.1 ng/m²), respectively. Full article

Background/Objectives: Epidemiological and clinical studies have linked both hypothyroidism and hyperthyroidism to adverse cardiac outcomes, including heart failure and myocardial fibrosis. Triiodothyronine (T3), a biologically active thyroid hormone, is important for cardiovascular homeostasis. While the effects of physiological and non-physiological T3 levels on cardiomyocytes have been extensively investigated, the impact of hypothyroidism and hyperthyroidism on cardiac stromal cells (CSCs), which constitute the majority of the cells in the heart, remains understudied. Given CSCs’ essential role in extracellular matrix (ECM) remodeling and paracrine signaling, understanding their response to altered T3 states is necessary to fully elucidate the thyroid hormone-induced cardiac responses. Methods: Cardiac stromal cells were isolated from human atrial appendages and cultured under hypothyroid (0 nM T3), euthyroid (2.5 nM T3), and hyperthyroid (25 nM T3) conditions for 24 (short term) and 120 h (long term). The cells were harvested after 24 h of treatment using trypsin and automatically counted, and their ECM-related gene and growth factor expression levels were assessed using quantitative RT-PCR. Cardiac glucose uptake in hypothyroid, euthyroid, and hyperthyroid mice was monitored using [18F]-FDG PET/CT at acute (7 days) and chronic (42 days) time points. Results: Both hypo- and hyperthyroidism significantly increased the number of CSCs harvested after 24 h. There were acute alterations in the expression of the ECM-related genes COL1A1, COL3A1, TIMP3 (p < 0.05), and TIMP1 (p < 0.01). Similarly, growth factors such as PDGF-A (p < 0.001), TGF-b, and IGF1 (p < 0.05) were transiently upregulated under non-physiological T3 conditions, especially hypothyroidism. Most of these alterations were attenuated or reversed at the 120 h time point. In vivo PET imaging revealed significant increases in cardiac glucose uptake under acute hypothyroidism (p < 0.05) and decreases under acute hyperthyroidism (p < 0.05). However, these metabolic shifts normalized with chronic exposure, paralleling the transient nature of the gene expression changes observed in vitro. Conclusions: Non-physiological T3 concentrations induce proliferation and changes in ECM-related and growth factor gene expression in CSCs. Most of these changes are acute and return to normal levels after chronic exposure. These transient cellular responses correlate closely with the cardiac metabolic response patterns to acute and chronic hypothyroidism and hyperthyroidism. Full article

Introduction: Pneumonitis represents one of the clinically significant adverse events observed in patients with non-small-cell lung cancer (NSCLC) who receive durvalumab as consolidation therapy after chemoradiotherapy (CRT). Although clinical factors such as radiation dose (e.g., V20) and interstitial lung abnormalities (ILAs) have been reported as risk predictors, accurate and objective prognostication remains difficult. This study aimed to develop a radiomics-based machine learning model to predict grade ≥ 2 pneumonitis. Methods: This retrospective study included patients with unresectable NSCLC who received CRT followed by durvalumab. Radiomic features, including first-order and texture and shape-based features with wavelet transformation were extracted from whole-lung regions on pre-durvalumab computed tomography (CT) images. Machine learning models, support vector machines, k-nearest neighbor, neural networks, and naïve Bayes classifiers were developed and evaluated using a testing cohort. Model performance was assessed using five-fold cross-validation. Conventional predictors, including V20 and ILAs, were also assessed using logistic regression and receiver operating characteristic analysis. Results: Among 123 patients, 44 (35.8%) developed grade ≥ 2 pneumonitis. The best-performing model, a support vector machine, achieved an AUC of 0.88 and accuracy of 0.81, the conventional model showed lower performance with an AUC of 0.71 and accuracy of 0.64. Conclusions: Radiomics-based machine learning demonstrated superior performance over clinical parameters in predicting pneumonitis. This approach may enable individualized risk stratification and support early intervention in patients with NSCLC. Full article

Background/Objectives: Primary central nervous system lymphoma (PCNSL) has a markedly high proliferation rate, making early diagnosis and prompt therapeutic intervention essential. To accelerate diagnosis, our institution adopted flow cytometry (FCM) in conjunction with conventional histopathology, and this study therefore evaluated the diagnostic performance of FCM for PCNSL. Methods: We retrospectively analyzed 67 consecutive patients with suspected PCNSL who underwent intraoperative FCM between 2010 and 2023 based on preoperative imaging. B-cell clonality was defined as ≥20% CD19/CD20-positive cells with a κ/λ ratio of >3.0 or <0.5. Results: Using histopathology, we confirmed the presence of PCNSL in 42 patients, all diagnosed as having diffuse large B-cell lymphoma. Six cases (14.3%) were discordant (FCM-D). The sensitivity, specificity, and positive predictive value of FCM were 85.7%, 100%, and 100%, respectively. T-cell markers were significantly elevated in FCM-D cases (p < 0.01), although these were pathologically diagnosed as diffuse large B-cell lymphoma based on histology and immunohistochemistry. Conclusions: FCM yields reliable diagnostic information within hours of tissue collection and supports early therapeutic decisions in PCNSL. Discordant results may reflect reactive T-cell infiltration. This is the first study to present detailed subset analyses in PCNSL using FCM in correlation with pathology, underscoring its utility as a rapid diagnostic tool. Full article

In G. E. M. Anscombe’s extensive correspondence with G. H. von Wright, one of the many topics that come up is the bombing of Hiroshima and Nagasaki at the end of World War II. What she says in these letters is significant because of the interest in what she wrote elsewhere about the use of atomic weapons. It is especially interesting because she might seem to imply here that only a person with religious faith is capable of being just. This paper quotes the relevant passages from the correspondence, explores what she might have meant, and concludes that she is not committed to the view that only the faithful can be just. Full article

Background/Objectives: 5-Aminolevulinic acid (5-ALA) is a biosynthetic precursor of heme that induces heme oxygenase-1 (HO-1). Therapeutic induction of HO-1 has shown effectiveness in various autoimmune disease models, including type 1 diabetes (T1D). However, the efficacy of 5-ALA as an HO-1 inducer in T1D models remains unexplored. This study aimed to investigate the therapeutic efficacy of oral 5-ALA administration in preventing autoimmune diabetes development in nonobese diabetic (NOD) mice. Methods: We evaluated diabetes incidence, levels of insulin autoantibody, and severity of insulitis in 5-ALA-treated and control NOD mice. HO-1 expression of dendritic cells in the pancreatic islets and spleen of 5-ALA-treated NOD mice was measured. The IFN-γ/IL-17 of islet-infiltrating T cells and IL-10/IL-12 productions of dendritic cells in the spleen of 5-ALA-treated NOD mice were assessed. We stimulated islet antigen-specific CD4⁺ T cells with islet antigen-pulsed dendritic cells in the presence of 5-ALA and examined the proliferation of the T cells. Finally, we adoptively transferred islet antigen-specific CD4⁺ T cells into 5-ALA-treated, immunodeficient NOD-Rag1 knockout mice, and diabetes incidence in recipients was determined. Results: Oral 5-ALA treatment did not significantly impact diabetes incidence, levels of insulin autoantibody, and insulitis. No significant difference was observed in HO-1 expression in dendritic cells and cytokine production of T cells and dendritic cells. Similarly, there was no significant difference in the proliferation of islet antigen-specific CD4⁺ T cells in vitro and diabetes induction in transfer experiments. Conclusions: Oral administration of 5-ALA has a limited effect on suppressing the development of autoimmune diabetes in NOD mice. Full article

To reduce environmental contamination following the release of various radionuclides during the Fukushima Daiichi Nuclear Power Plant accident, the Japanese government has continued decontamination work and decided to use interim storage facilities (ISFs) in the towns of Okuma and Futaba to house large quantities of contaminated soil and waste until their final disposal. This study aims to clarify whether there are differences in the acceptance of removed soil for recycling between people who provided land for ISFs and those who do not. Furthermore, we analyzed the risk perception of the radiation effects on offspring, trust in information from public authorities, and intention to return to their hometown. A questionnaire survey was conducted at Okuma and Futaba town homes in the ISF area. Compared with those who did not provide land to the ISFs (n = 538, 68.0%), people who provided land (n = 141, 77.9%) responded that they were accepting the building of the ISFs (p = 0.018). Meanwhile, approximately half of the respondents were “unable to decide” concerning the recycling of removed soil in their current region of residence regardless of whether the land provided or not. Similarly, there were no significant differences between the groups regarding radiation risk perceptions of the offspring effects on residents and intention to return, or whether to provide land to the ISFs. The study suggests that it is important to continue radiation risk communication to determine whether people have provided land to the ISFs. Full article

This study investigates the pathophysiological process of healed perforated corneal ulcers (HPCUs) in humans. All subjects underwent keratoplasty due to opacities or leakage from HPCUs. Half of each specimen was fixed with 4% glutaraldehyde for transmission electron microscope (TEM) examination. The other half was fixed in 10% formaldehyde for immunofluorescence (IF) examination. TEM identified layered structures with two cell types (polygonal and elongated) connected by gap or adherent junctions during early stage of healing. Both apoptotic and mitotic changes were found in both types of cells. There were no endothelial cells or Descemet’s membrane (DM) present in early stage of healing. During the intermediate stage, the healed area comprised three layers: epithelium, Bowman’s layer, and stroma, with an increase in stromal collagen. Later, adjacent endothelial cells crept in, forming DM and completing the cornea’s 5-layer structure. IF examinations revealed that vimentin⁺ and α-smooth muscle actin (αSMA)⁺ myofibroblasts gathered around the damaged site. Proliferating cell nuclear antigen⁺ cells, which indicated cell proliferation, were found in both cells. Anti-phospho-histone H2AX antibodies were found in some epithelial cells. CK14-positive cells were only found in superficial polygonal cells. Corneal wound healing is a complex process that includes apoptosis, cell migration, mitosis, differentiation, and extracellular matrix remodeling. Full article

Background/Objectives: Effective management of aneurysmal subarachnoid hemorrhage (aSAH) requires an evidence-based treatment protocol. This study examines the outcomes of a unified, multicenter protocol emphasizing postoperative clazosentan as the first-line treatment for vasospasm. Methods: A standardized protocol prioritizing systemic management with clazosentan for vasospasm was implemented in April 2023. Cases treated between April 2022 and March 2024 were categorized into four groups: preprotocol fasudil treatment (PrF), preprotocol clazosentan treatment (PrC), postprotocol fasudil treatment (PoF), and postprotocol clazosentan treatment (PoC); these groups were analyzed. Results: Among 407 registered cases, 322 were eligible for analysis (PrF, 128; PrC, 69; PoF, 28; PoC, 97). PoC exhibited significantly lower angiographic vasospasm rates and had a lower incidence of symptomatic vasospasm compared with PrF (p = 0.048, p = 0.057). Logistic regression identified the clazosentan protocol as a predictive factor for vasospasm reduction (p = 0.02, OR 0.46 [0.22–0.94]; p = 0.022, OR 0.38 [0.16–0.91]). PoC experienced less fluid retention than the PrC (p < 0.001). Logistic regression confirmed protocol adherence with protocol reduced complications (p < 0.001, OR 0.24 [0.11–0.52]), included fluid retention (p < 0.001, OR 0.088 [0.03–0.29]). In older patients, no significant differences in vasospasm or complications were observed between PrF and PoC, but a trend toward reduced complications was observed in World Federation of Neurosurgical Societies (WFNS) grade V cases. Conclusions: Clazosentan-first protocol effectively reduces vasospasm and complications in aSAH management. It is also safe for older patients and those with WFNS grade V, offering a promising treatment strategy. Full article

To understand the biological effects of residual radioactivity after the atomic bomb explosion in Hiroshima and Nagasaki, we previously investigated the effects of ⁵⁶Mn, a major residual radioisotope. Our rat study demonstrated that inhalation exposure to ⁵⁶MnO₂ microparticles affected gene expression in the lungs, testes, and liver, despite the low radiation doses. Because ⁵⁶Mn is a β- and γ-emitter, the differential effects between β- and γ-rays should be clarified. In this study, ³¹Si, a β-emitter with a radioactive half-life similar to that of ⁵⁶Mn, was used to determine its effects. Male Wistar rats were exposed to sprayed neutron-activated ³¹SiO₂ microparticles, stable SiO₂ microparticles, or X-rays. The animals were examined on days 3 and 14 after irradiation. The expression of radiation-inducible marker genes, including Ccng1, Cdkn1a, and Phlda3, was measured in the spleen, lungs, and liver. Furthermore, the expressions of pathophysiological marker genes, including Aqp1, Aqp5, and Smad7 in the lungs and Cth, Ccl2, and Nfkb1 in the liver, were determined. Impacts of ³¹SiO₂ exposure were observed mainly in the liver, where the expression of Cth markedly increased on post-exposure days 3 and 14. Our data suggest that internal exposure to β-emitted microparticles has significant biological effects and its possible roles as residual radiation after atomic bombing. Full article

Childhood radiation is a risk factor for thyroid cancer that became well known after the Chernobyl nuclear plant accident. Although these human cases have been extensively studied, the mechanisms underlying childhood susceptibility to radiation-induced thyroid cancer have yet to be explained. Our previous study showed that neonatal X-irradiation resulted in long-term alterations in the mRNA expression of thyroid cancer-related marker genes, which may be a critical mechanism for understanding the higher radiation sensitivity in young patients. In this study, RNA sequencing (RNA-Seq)-based gene expression analysis was employed to identify thyroid genes whose mRNA expression was changed by neonatal irradiation. Male Wistar rats aged 1 week and 4 months were subjected to cervical X-irradiation at 4 Gy. After 8 weeks, total RNA was extracted from the thyroid and subjected to RNA-Seq analysis to identify differentially expressed genes following irradiation. We identified five upregulated genes (i.e., Adm2, Vnn1, Snph, Gria3, and Cpa4) and one downregulated gene (i.e., Crtac1) explicitly altered by neonatal radiation exposure. Western blotting confirmed the corresponding changes in CPA4 and CRTAC1 expression. The gene expressions identified were also altered in thyroid tumors induced by an iodine-deficient diet. These long-term changes in thyroid gene expression caused by neonatal irradiation may be involved in the increased risk of thyroid carcinogenesis. Full article

The approach taken by Marvel and Hanna-Barbera to adapting Godzilla for a young American audience is a form of cultural appropriation. Cultural appropriation involves removing the subject from its cultural context. In this case, Marvel and Hanna-Barbera removed the character from its origin, where it emerged as a consequence of the atomic bomb. Gojira is first a scourge of Japan and later its savior against invasion from cosmic forces and nefarious kaiju. Godzilla is changed into what is ultimately a sanitized version of imperial inventory. The properties of the 1970s Godzilla, however, were not wholly negative. Indeed, they laid the foundation for an American rediscovery of the original Gojira film and its sequels, which have since been released in their original versions. This article will examine how Marvel Comics and Hanna-Barbera cartoons culturally appropriated Godzilla for American children, but how this also led to an appreciation of the Japanese films. Full article