Development of a non-destructive depth-selective quantification method for sub-percent carbon contents in steel using negative muon lifetime analysis.

The amount of C in steel, which is critical in determining its properties, is strongly influenced by steel production technology. We propose a novel method of quantifying the bulk C content in steel non-destructively using muons. This revolutionary method may be used not only in the quality control of steel in production, but also in analyzing precious steel archaeological artifacts. A negatively charged muon forms an atomic system owing to its negative charge, and is finally absorbed into the nucleus or decays to an electron. The lifetimes of muons differ significantly, depending on whether they are trapped by Fe or C atoms, and identifying the elemental content at the muon stoppage position is possible via muon lifetime measurements. The relationship between the muon capture probabilities of C/Fe and the elemental content of C exhibits a good linearity, and the C content in the steel may be quantitatively determined via muon lifetime measurements. Furthermore, by controlling the incident energies of the muons, they may be stopped in each layer of a stacked sample consisting of three types of steel plates with thicknesses of 0.5 mm, and we successfully determined the C contents in the range 0.20-1.03 wt% depth-selectively, without sample destruction.

Factors associated with cavity formation after stereotactic body radiation therapy for peripheral early-stage lung cancer.

PURPOSE: This retrospective study aimed to identify the factors associated with cavity formation after SBRT in peripheral early-stage lung cancer patients. We analyzed the occurrence of cavity changes after SBRT. MATERIALS AND METHODS: We examined 99 cases with T1-T2aN0 peripheral non-small cell lung cancer treated with SBRT from 2004 to 2021. Patients underwent respiratory function tests, including diffusing capacity for carbon monoxide (DLco), before treatment. The median observation period was 35 months (IQR 18-47.5 months). Treatment involved fixed multi-portal irradiation in 67% of cases and VMAT in 33%. The total radiation doses ranged from 42 to 55 Gy, delivered over 4 to 5 fractions. RESULTS: Cavity formation occurred in 14 cases (14.1%), appearing a median of 8 months after SBRT. The cavity disappeared in a median of 4 months after formation. High DLco and total radiation dose were identified as factors significantly associated with cavity formation. There have been no confirmed recurrences to date, but one patient developed a lung abscess. CONCLUSION: Although cavity formation after SBRT for peripheral early-stage lung cancer is infrequent, it can occur. This study showed high DLco and total radiation dose to be factors significantly associated with cavity formation. These findings can be applied to optimizing radiation therapy (RT) and improving patient outcomes. Further research is needed to determine the optimal radiation dose for patients with near-normal DLco for whom surgery is an option. This study provides valuable insights into image changes after RT.

PGC-1α regulates airway epithelial barrier dysfunction induced by house dust mite.

BACKGROUND: The airway epithelial barrier function is disrupted in the airways of asthmatic patients. Abnormal mitochondrial biogenesis is reportedly involved in the pathogenesis of asthma. However, the role of mitochondrial biogenesis in the airway barrier dysfunction has not been elucidated yet. This study aimed to clarify whether the peroxisome proliferator-activated receptor γ coactivator-1alpha (PGC-1α), a central regulator of mitochondrial biogenesis, is involved in the disruption of the airway barrier function induced by aeroallergens. METHODS: BEAS-2B cells were exposed to house dust mite (HDM) and the expressions of PGC-1α and E-cadherin, a junctional protein, were examined by immunoblotting. The effect of SRT1720, a PGC-1α activator, was investigated by immunoblotting, immunocytochemistry, and measuring the transepithelial electrical resistance (TEER) on the HDM-induced reduction in mitochondrial biogenesis markers and junctional proteins in airway bronchial epithelial cells. Furthermore,the effects of protease activated receptor 2 (PAR2) inhibitor, GB83, Toll-like receptor 4 (TLR4) inhibitor, lipopolysaccharide from Rhodobacter sphaeroides (LPS-RS), protease inhibitors including E64 and 4-(2-Aminoethyl) benzenesulfonyl fluoride hydrochloride (AEBSF) on the HDM-induced barrier dysfunction were investigated. RESULTS: The amounts of PGC-1α and E-cadherin in the HDM-treated cells were significantly decreased compared to the vehicle-treated cells. SRT1720 restored the expressions of PGC-1α and E-cadherin reduced by HDM in BEAS-2B cells. Treatment with SRT1720 also significantly ameliorated the HDM-induced reduction in TEER. In addition, GB83, LPS-RS, E64 and AEBSF prevented the HDM-induced reduction in the expression of PGC1α and E-cadherin. CONCLUSIONS: The current study demonstrated that HDM disrupted the airway barrier function through the PAR2/TLR4/PGC-1α-dependent pathway. The modulation of this pathway could be a new approach for the treatment of asthma.

Damage-less observation of polymers by electron dose control in scanning electron microscope.

Methodology for quantitative evaluation of electron radiation damage and calculation of tolerable electron dose was developed to achieve damage-less scanning electron microscope (SEM) observation of beam-sensitive polymer film. The radiation damage is typically evaluated with visual impressions of SEM images; however, this method may be unreliable because observer's subjectivity may affect the results. Evaluation with quantitative value is crucial to improve reliability. In this study, the radiation damage was evaluated by using normalized correlative coefficient (RNCC) between an initial frame and latter frames of the multiple SEM images that were taken consecutively. Tolerable dose was obtained by defining a threshold point of RNCC where rapid reduction of RNCC started. A SEM image with less damage and acceptable signal-to-noise ratio was obtained by integrating the images from the initial frame to the tolerable frame.

Successful treatment of nonsmall cell lung cancer patients with leptomeningeal metastases using whole brain radiotherapy and tyrosine kinase inhibitors.

The efficacy of treatments in patients with nonsmall cell lung cancer (NSCLC) with leptomeningeal metastases (LMs) remains unclear. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) play an important role in the treatment of patients with NSCLC. However, few studies have investigated the efficacy of combination therapy with TKIs and whole brain radiotherapy (WBRT) in patients with NSCLC/LM. We report here the case of a male patient in his 60s with adenocarcinoma who underwent lobectomy of the right upper lobe. The cancer was classified as pT1bN1M0 Stage IIA, and a mutational analysis revealed the presence of an EGFR mutation. However, 6 months after standard chemotherapy, LM had developed and WBRT was administered. Gefitinib (250 mg/day) was administered after WBRT. The patient remained free of significant recurrent disease for 57 months after WBRT was administered. Combination therapy with TKIs and WBRT is associated with relatively long survival times in patients with LM.

N-terminal [Glu]3 moiety of γ-glutamyl peptides contributes largely to the activation of human calcium-sensing receptor, a kokumi receptor.

γ-glutamyl peptides have been suggested to impart kokumi properties to foods by activating human calcium-sensing receptor (hCaSR). In this study, the relationship between γ-glutamyl peptide structure and hCaSR activity was systematically analyzed using γ-[Glu](n=0-4)-α-[Glu](n=0-3)-Tyr. Our results suggest that N-terminal [Glu]3 moiety is very important for hCaSR activities of γ-glutamyl peptides.

A case of localized tracheobronchial relapsing polychondritis with positive matrilin-1 staining.

BACKGROUND: Relapsing polychondritis (RPC) is a rare progressive autoimmune disease characterized by inflammation in the cartilage of multiple organs. Tracheobronchial involvement appears in nearly half of RPC patients during the course of their disease and represents the main cause of death. Localized tracheobronchial RPC is much rarer, and the pathogenesis remains unclear. Matrilin-1 is a non-collagenous cartilage matrix protein and has been suggested to be a potent autoantigen that induces the airway disease of RPC in animal models. However, the expression of matrilin-1 in tracheobronchial tissue in human remains unclear. Therefore, we examined the expression of matrilin-1 in the tracheal and auricular tissues in a localized tracheobronchial RPC patient. CASE PRESENTATION: A 62-year-old man with systemic sclerosis presented with cough and dyspnea on exertion. The lung function test showed an expiratory flow limitation and chest computed tomography showed diffuse thickness from the trachea to the bronchiole. No other tests showed abnormal findings. To evaluate further, bronchoscopy was performed and endobronchial ultrasonography showed thickness in the fourth-marginal echo layer suggesting inflammation of the cartilage. However, the tracheal biopsy showed no specific findings. The subsequent surgical tracheal biopsies showed inflammatory cell infiltration with destruction of the cartilage. Neither auricular nor nasal deformity, except for a tracheobronchial lesion, was detected. Biopsy from the left auricular cartilage also did not show any inflammatory changes. Finally, we diagnosed the patient with localized tracheobronchial RPC. To address the hypothesis that autoimmunity against matrilin-1 is involved in the pathogenesis of localized tracheobronchial RPC, we evaluated the expression level of matrilin-1 in a tracheal and auricular specimen from this patient. Immunohistochemical staining with anti-matrilin-1 antibody showed matrilin-1 in the tracheal but not in the auricular cartilage. CONCLUSIONS: We first demonstrated the expression of matrilin-1 in tracheal but not in auricular cartilage in a localized tracheobronchial RPC patient. This result supports the possibility that matrilin-1 is involved in the pathogenesis of localized tracheobronchial RPC. However, this is only one case report and further observations will be needed to confirm this result.

Sweet proteins lysozyme and thaumatin are protein-type agonists for the calcium-sensing receptor.

In addition to the maintenance of Ca2+ homeostasis, the calcium-sensing receptor (CaSR) is involved in many diverse physiological functions in the mammalian body. The receptor works as a kokumi taste receptor in taste buds and as a nutrient sensor in the gut, where it regulates the secretion of glycemic response and appetite-related hormones. To identify novel human CaSR (hCaSR) activators from food ingredients, we conducted a screening using a cell-based hCaSR assay. Hen egg-white lysozyme, which is a sweet protein, was found to be a novel orthosteric agonist of hCaSR with an EC50 value of 592 µM. Lysozyme hydrolysate was not able to activate hCaSR, thus suggesting that the protein structure of lysozyme is necessary for hCaSR activation. Thaumatin, which is another sweet protein, also activated hCaSR with an EC50 value of 71 µM. This is the first report that shows hCaSR activation by proteins with molecular weights exceeding 10,000 Da. These results provide a new avenue for the development of hCaSR activators, which could be applicable in food or drugs that modulate taste perception, appetite, or glucose tolerance, in addition to Ca2+ homeostasis.

Roles of Ki-67 and p16 as biomarkers for unknown primary head and neck squamous cell carcinoma.

PURPOSE: Treatment guidelines have not been established for unknown primary head and neck squamous cell carcinoma (SCC). For these patients, chemoradiotherapy (CRT) can provide a better prognosis than that for patients with other head and neck cancers. The presence of HPV in the tumor is associated with a better outcome. However, not all patients with HPV-positive unknown primary head and neck SCC experience good treatment outcomes in actual clinical settings. METHODS: We thus retrospectively determined the Ki-67 proliferation index and p16 expression status to assess the associations of these parameters with treatment outcomes of patients with unknown primary head and neck SCC. RESULTS: The subjects were 13 patients who underwent CRT after surgery or excision biopsy between 1999 and 2016. The 2- and 5-year overall survival (OS) rate was 76.9% and 68.4%, respectively. The prognostic factor was age. There was no significant difference in survival between patients with a high Ki-67 vs. low Ki-67 or between patients with p16-positive vs. p16-negative metastases OS. However, all p16-positive patients with low Ki-67 showed good locoregional control. CONCLUSIONS: The combination of ki67 expression and p16 expression status may allow prediction of local control more accurately than p16 expression status alone.

Spontaneous ureteral rupture caused by iliac aneurysm: a case report.

BACKGROUND: Rupture of the ureter with extravasation resulting from an iliac aneurysm is extremely rare. Herein, we report a case of ureteric rupture with urinary extravasation secondary to an iliac aneurysm. CASE PRESENTATION: An 80-year-old man was admitted to our hospital for sudden onset of severe abdominal pain. Contrast-enhanced computed tomography demonstrated a large left internal iliac aneurysm (6.5 cm in diameter) and a ureteric rupture with leakage of contrast media from the left ureter, indicating a spontaneous ureteral rupture. The patient was treated with placement of a ureteral double-J stent under endoscopic and X-ray fluoroscopic guidance and endovascular aortic repair. His postoperative course was uneventful and he was discharged on postoperative day 20. A computed tomography scan at 2 weeks after surgery showed no contrast extravasation from the ureter or end leak. CONCLUSION: Combination treatment with ureteral and endovascular stenting is effective in avoiding aneurysmal rupture and the serious consequences of a ureteral rupture, which include a perinephric or retroperitoneal collection, abscess formation, subsequent urosepsis, and graft infection.

Dietary soybean protein ameliorates high-fat diet-induced obesity by modifying the gut microbiota-dependent biotransformation of bile acids.

The consumption of soybean protein has well-known favorable metabolic effects (e.g., reduced body weight, body fat, hyperglycemia, insulin resistance, hepatic steatosis, and lipogenesis). These effects of soy protein have been linked to modulation by the gut microbiota; however, the dynamic interplay among these factors remains unclear. Accordingly, we examined the metabolic phenotype, intestinal BA pool, and the gut microbiome of male C57BL/6 mice that were randomized to receive either a regular high-fat diet (HFD) or HFD that contained soybean protein isolate (SPI) in place of dairy protein. The intake of SPI significantly reduced the HFD-induced weight gain and adipose tissue mass accumulation and attenuated hepatic steatosis. Along with an enhancement in the secretion of intestinal Glucagon-like peptide-1 (GLP-1), an enlarged cecal BA pool with an elevated secondary/primary BA ratio was observed in the mice that consumed SPI, while fecal BA excretion remained unaltered. SPI also elicited dramatic changes in the gut microbiome, characterized by an expansion of taxa that may be involved in the biotransformation of BAs. The observed effects were abolished in germ-free (GF) mice, indicating that they were dependent on the microbiota. These findings collectively indicate that the metabolic benefits of SPI under the HFD regime may arise from a microbiota-driven increase in BA transformation and increase in GLP-1 secretion.

Clinical results of multimodality therapy for esophageal cancer with distant metastasis.

BACKGROUND: The purpose of this study is to evaluate outcomes in upfront local response and survival of patients with esophageal cancer and distant metastasis. METHODS: This retrospective study included 34 patients (25 males) aged 42-92 years (median, 70 years) with a histological diagnosis of esophageal squamous cell cancer with distant metastasis. Staging was performed according to the UICC's TNM (6th edition) classification of malignant tumor. RESULTS: The median survival time (MST) was 5 months. The 1-year overall survival (OS) was 20.6%. Improved OS was associated with receipt of surgery [hazard ratio (HR), 3.857; 95% CI, 1.142-13.024; P=0.030] on both univariate and multivariate analyses, and the MST was 11 months. The overall objective local response rate was 82%. Ten patients had complete response (CR), 18 had partial response (PR). The overall symptom response was 88% patients. Six had CR, 24 had PR. There was no significant difference in the objective and symptom response between ≤50 and >50 Gy. Concurrent chemoradiotherapy (CCRT) with 50 Gy gave results of objective and symptom responses comparable to those of 60 Gy, which has been reported previously. CONCLUSIONS: CCRT with 50 Gy gave results comparable to those of 60 Gy, which has been reported previously, and the toxicity was acceptable. Our findings showed that a multimodality therapy that includes surgery may improve survival in only a select group.

Significance of stereotactic body radiotherapy in older patients with early stage non-small cell lung cancer.

OBJECTIVES: Our aim was to investigate long-term treatment outcomes in older patients with early stage non-small cell lung cancer (NSCLC) and the presence or absence of therapeutic benefits, using the G8 screening tool. METHODS: We retrospectively studied 43 older patients (median age 78 years, range 65-89 years) with stage I lung tumors (T1 and T2 tumors in 34 and 9 patients, respectively), who underwent stereotactic body radiotherapy (SBRT). This study assessed outcomes in a cohort of patients who received geriatric assessments, performed between 2004 and 2011, before the start of their SBRT regimen. Any questions asked to patients before undergoing treatment were applied to the G8 screening tool. RESULTS: G8 scores ranged from 8 to 16 (median, 12) in all patients (n = 43), while G8 scores in the T1 and T2 groups ranged from 9 to 16 (median, 13) and 8 to 15 (median, 12), respectively. In patients with G8 scores ≤12, the 2-year and 5-year survival rates were 56.1% and 28% respectively, while the rates were 94.1% and 68.4%, respectively, in patients with G8 scores ≥13 (P = 0.0014). During long-term follow-up, 25.9% of the patients (n = 43) died of the primary disease, NSCLC, and 34.9% of patients died of other diseases or other types of cancer. CONCLUSION: SBRT may be effective, even in older adults. Regardless of age, SBRT improved the long-term survival of patients only with G8 scores ≥13. The G8 screening tool may aid in determining whether older patients with comorbidities would benefit from SBRT.

Clinical Outcomes of Hypopharyngeal Cancer Receiving Definitive Radiotherapy with Concurrent Chemotherapy.

AIM: To evaluate clinical outcomes of concurrent chemoradiotherapy (CCRT) in patients with hypopharyngeal cancer (HPC). PATIENTS AND METHODS: This retrospective study included 80 patients (75 males) aged 48 to 78 years (median=66 years) with a histological diagnosis of HPC. The 5-fluorouracil and cisplatin (FP) regimen was used until 2007 and then switched to the docetaxel, cisplatin, and 5-fluorouracil (TPF) regimen. Radiotherapy was administered to a total dose of 60 to 72 Gy (median=66 Gy). RESULTS: The 5-year overall survival and disease-free survival rates were 49.3% and 60.7%, respectively. Improved disease-free survival was associated with lower N-stage (hazard ratio=0.249; 95% confidence interval=0.096-0.643; p=0.041). CONCLUSION: There were no significant differences in overall and disease-free survival between patients receiving CCRT with the TPF regimen and those who received FP for a long period of treatment but did not finish two courses.

Various Regimens of Total Body Irradiation for Hematopoietic Stem Cell Transplant.

OBJECTIVES: We aimed to evaluate the safety of total body irradiation before bone marrow transplant. MATERIALS AND METHODS: We analyzed 110 patients (65 male, 45 female) who underwent total body irradiation for hematopoietic stem cell transplant between May 1998 and March 2013. Median age at total body irradiation was 17 years (range, 1-62 y). Median observation time was 777 days (range, 31-5494 d). Initial diagnoses were acute lymphoblastic leukemia (24 patients), acute myeloid leukemia (26 patients), chronic myeloid leukemia (7 patients), myelodysplastic syndrome (8 patients), malignant lymphoma (13 patients), mucopolysaccharidosis (12 patients), neuroblastoma (10 patients), and other diseases (10 patients). The total fractionated dose used for total body irradiation was 12 Gy in 69 patients and 6.0-10.8 Gy in 29 patients. Single-dose total body irradiation was administered to 12 patients. Most patients (63 of 110) received chemotherapy consisting of cyclophosphamide alone. RESULTS: Ocular complications were observed in 29.5% of the patients. Hypothyroidism, interstitial pneumonia, obliterative bronchiolitis, and veno-occlusive disease developed in 8.2%, 1.8%, 0.9%, and 2.7% of patients. Growth abnormality was observed in 10 (20%) of the 50 pediatric patients. The use of a lower dose (< 12 Gy vs 12 Gy) of fractionated total body irradiation did not decrease the incidence of adverse events; however, nonmyeloablative conditioning with low-dose singlefraction total body irradiation reduced the incidence of adverse events. Three patients who underwent total body irradiation as reirradiation therapy achieved long-term survival without adverse events. CONCLUSIONS: Fractionated total body irradiation given at a lower dose (<12 Gy vs 12 Gy) did not decrease the incidence of adverse events.

Clinical Results for Bladder Cancer Treated by Radiotherapy Without Concurrent Standard Chemotherapy.

AIM: To evaluate clinical outcomes of three-dimensional conformal radiotherapy (3D-CRT) alone in patients with bladder cancer who were unfit for concurrent standard chemotherapy. PATIENTS AND METHODS: Between January 2007 and May 2016, 34 patients (20 men, 14 women) aged 65-97 years (median=83) with bladder cancer cT1-4bN0-1M1 were treated with conformal whole-bladder radiotherapy with fractions of 1.8-3 Gy up to a total dose of 40-50 Gy. RESULTS: Median survival was 10 months (range=1-99); 1-year and 3-year survival was 51.4% and 34.3%, respectively. Radiation dose >50 Gy was associated with improved survival. Three-year local control (LC) rate was 58.8%. On multivariate analysis, only radiation dose showed a significant association with LC. CONCLUSION: Our results demonstrated the safety and feasibility of radiotherapy in patients with bladder cancer unfit for concurrent standard chemotherapy. A higher radiation dose may confer superior LC and overall survival (OS) without complications.

Treatment outcomes of patients with small cell lung cancer without prophylactic cranial irradiation.

BACKGROUND: Prophylactic cranial irradiation (PCI) is indicated for limited disease (LD) in small cell lung cancer (SCLC) patients who achieve a complete or near-complete response; however, it is sometimes not administered because of possible adverse reactions or patient refusal. Here we assessed treatment outcomes among patients with SCLC who were not treated with PCI. METHODS: The medical records of 60 patients (45 men, 15 women; mean age, 68 years; age range, 51-82 years) with SCLC were retrospectively reviewed. The tumors were staged by TNM classification. Two, 2, 5, 4, 32, and 15 patients had stage IA, IB, IIA, IIB, IIIA, and IIIB tumors, respectively. The patients were treated with thoracic radiotherapy (TRT) and four courses of chemotherapy. RESULTS: Our subjects had a median survival of 25 months and 2- and 5-year survival rates of 52.6% and 25.3%, respectively. Univariate analysis revealed that the development of brain metastasis, performance status (PS), and T-stage were significant factors correlated with survival rate. Multivariate analysis identified only PS [hazard ratio (HR), 5.845, 95% confidence interval (CI), 2.333-14.63, P=0.002] and brain metastasis as independent prognostic variables (HR, 2.344, 95% CI, 1.071-5.128, P=0.033). CONCLUSIONS: The results of our study demonstrated that the outcomes of treatment without PCI were improved, as compared with those of previously published data. Our findings may be used as reference data when PCI cannot be performed.

Successful radiotherapy in postoperative recurrence of a primary mediastinal yolk sac tumor: A case report.

A woman in her 60s was evaluated for anterior chest pain. Computed tomography (CT) revealed a 50 mm mass with irregular contrast enhancement in the anterior mediastinum. α-fetoprotein (AFP) level was elevated to 1188 ng/mL. A germ cell tumor was diagnosed, mostly comprising of a yolk sac tumor (YST). Two courses of chemotherapy with cisplatin (CDDP) and etoposide (VP16) were administered and surgical tumor resection was then performed. The final diagnosis was YST. CDDP and VP16 were continued postoperatively; however, because the AFP level increased about six months after surgery, the chemotherapy regimen was altered to bleomycin and CPT-11. As the AFP again increased and a CT scan revealed tumor re-enlargement, recurrent YST was diagnosed and radiotherapy was administered. The patient received a total of 60 Gy (2 Gy per fraction). The tumor started to shrink during radiotherapy and AFP levels decreased. By one month post-radiotherapy, AFP levels had normalized and the tumor had disappeared. As of six years after radiotherapy, the patient remains alive without recurrence. Mediastinal YSTs are rare, and treatment usually includes surgery and preoperative and postoperative chemotherapy with cisplatin-based regimens. Successful treatment with radiotherapy has occasionally been reported. Our patient showed recurrence of a YST after surgery and chemotherapy, but achieved long-term survival after radiotherapy. Few patients with YST have undergone radiotherapy, but this approach was successful in our patient. In cases of postoperative recurrent YST resistant to chemotherapy, radiotherapy, together with salvage surgery, may offer a valuable option.

Radiation Therapy and Palliative Care Prolongs the Survival of Hepatocellular Carcinoma Patients with Bone Metastases.

Objective In recent years, an increase has been observed in the incidence of bone metastases from hepatocellular carcinoma (HCC). In 2007, our institution established a team approach, which includes the provision of palliative care. In the present study we evaluate the effects of palliative care on the prognosis of HCC patients with bone metastases. Methods The subjects included 44 patients with bone metastases who were treated with radiotherapy between 2000 and 2014. The subjects were divided into groups that received radiotherapy from 2000 to 2006 and after 2007. The overall survival rates after radiotherapy were analyzed. Results The median survival time of the patients who received care between 2007 and 2014 was 6 months, which was significantly longer than that in the patients who received care between 2000 and 2006. Conclusion The present team approach in our hospital, which includes the provision of palliative care, started in 2007. This approach may have improved prognosis of patients with metastatic HCC.