Quality of palliative radiotherapy assessed using quality indicators: a multicenter survey†.

We sought to identify potential evidence-practice gaps in palliative radiotherapy using quality indicators (QIs), previously developed using a modified Delphi method. Seven QIs were used to assess the quality of radiotherapy for bone metastases (BoM) and brain metastases (BrM). Compliance rate was calculated as the percentage of patients for whom recommended medical care was conducted. Random effects models were used to estimate the pooled compliance rates. Of the 39 invited radiation oncologists, 29 (74%) from 29 centers participated in the survey; 13 (45%) were academic and 16 (55%) were non-academic hospitals. For the QIs, except for BoM-4, the pooled compliance rates were higher than 80%; however, for at least some of the centers, the compliance rate was lower than these pooled rates. For BoM-4 regarding steroid use concurrent with radiotherapy for malignant spinal cord compression, the pooled compliance rate was as low as 32%. For BoM-1 regarding the choice of radiation schedule, the compliance rate was higher in academic hospitals than in non-academic hospitals (P = 0.021). For BrM-3 regarding the initiation of radiotherapy without delay, the compliance rate was lower in academic hospitals than in non-academic hospitals (P = 0.016). In conclusion, overall, compliance rates were high; however, for many QIs, practice remains to be improved in at least some centers. Steroids are infrequently used concurrently with radiotherapy for malignant spinal cord compression.

Comparison of pain-relieving effects by number of irradiations, through propensity score matching and the international consensus endpoint.

Background: Palliative radiotherapy for bone metastases utilizes various dose fractionation schedules. The pain-relieving effects of a single fraction (SF) and multiple fractions (MF) are largely debated due to the difficulty in matching patients' backgrounds and in assessing the effectiveness of pain relief. This study aimed to compare the pain-relieving effects of SF and MF palliative radiotherapy for bone metastases using propensity score matching and the international consensus endpoint (ICE). Materials and methods: Our study included 195 patients irradiated for bone metastasis. The primary endpoint was the pain-relieving effects used by ICE. In addition, the evaluation was performed by using responder (complete response/partial response) and non-responder (pain progression/indeterminate response) categorization. The secondary endpoints were the discharge or transfer rate at one month after irradiation and postirradiation pathological fracture rate. Propensity score matching was used to adjust patient's characteristics and reduce selection bias. Results: After adapting propensity score matching, the total number of patients was 74. There was no significant difference in the pain-relieving effects between SF and MF (p = 0.184). There were no significant differences in them between SF and MF when using responder and non-responder categorization (p = 0.163). Furthermore, there were no differences in the discharge or transfer rates (p = 0.693) and pathological fracture rates (p = 1.00). Conclusions: The combination of propensity score matching and ICE revealed no significant difference in the pain-relieving effects between SF and MF for bone metastases, thus, SF has no significant disadvantage compared to MF in pain-relieving effects.

Entomopathogenic fungus Beauveria bassiana-based bioinsecticide suppresses severity of powdery mildews of vegetables by inducing the plant defense responses.

The entomopathogenic fungus Beauveria bassiana is used commercially as a microbial insecticides against a wide range of agricultural insect pests. Some strains of B. bassiana protect the plants from pathogens, but the underlying mechanisms are largely unknown. Here, we found that prophylactic sprays of commercial bioinsecticide Botanigard on cucumber, tomato, and strawberry plants suppressed the severity of economically damaging powdery mildews. On leaf surfaces, hyphal elongation and spore germination of cucumber powdery mildew, Podosphaera xanthii, were inhibited, but B. bassiana strain GHA, the active ingredient isolated from Botanigard, only inhibited hyphal elongation but had no effect on spore germination of P. xanthii. In addition, strain GHA suppressed powdery mildew symptoms locally, not systemically. Treatment with Botanigard and strain GHA induced a hypersensitive response (HR)-like cell death in epidermal cells of the cucumber leaves in a concentration-dependent manner and inhibited penetration by P. xanthii. Transcriptome analysis and mass spectrometry revealed that GHA induced expression of salicylic acid (SA)-related genes, and treatment with Botanigard and GHA increased the SA level in the cucumber leaves. In NahG-transgenic tomato plants, which do not accumulate SA, the biocontrol effect of tomato powdery mildew by GHA was significantly reduced. These results suggested that B. bassiana GHA induces SA accumulation, leading to the induction of HR-like cell death against powdery mildew and subsequent suppression of fungal penetration. Thus, Botanigard has the potential to control both insect pests and plant diseases.

Increased Interleukin-36ß Expression Promotes Angiogenesis in Japanese Atopic Dermatitis.

While atopic dermatitis (AD) is considered as a T helper 2 (Th2)-centered disease, an increase in other types of inflammatory cytokines is also noted in AD and they may also contribute to the development of the disease. Recently, the efficacy of an anti-IL-36 receptor antibody in AD was demonstrated in a clinical trial. Although there have been several reports on IL-36α and IL-36γ expression and function in AD, IL-36ß has been barely studied. In this report, we examined IL-36ß expression and function using clinical samples of AD and the epidermal keratinocyte cell line, HaCaT cells. We demonstrated that IL-36ß expression in epidermal keratinocytes was increased in AD lesional skin compared to healthy skin. IL-36ß promoted vascular endothelial growth factor A production in HaCaT keratinocytes through phosphorylation of extracellular signal-regulated kinases 1 and 2. In addition, IL-36ß up-regulated placental growth factor mRNA expression in HaCaT keratinocytes. IL-36ß expression levels in epidermal keratinocytes were correlated with the number of dermal vessels in AD skin. These results suggest that IL-36ß may play an important role for angiogenesis in lesional skin of AD and that IL-36ß can be a therapeutic target in AD.

A Novel Medium for Isolating Two Japanese Species in the Fusarium graminearum Species Complex and a Dipstick DNA Chromatography Assay for Species Identification and Trichothecene Typing.

Members of the Fusarium graminearum species complex (Fg complex) are the primary pathogens that cause Fusarium head blight in wheat and barley. Fg complex members grow poorly on Fusarium oxysporum-selective media, such as Komada and Fo-G2, that have also been used for the isolation of other Fusarium species. Therefore, Komada medium was modified as FG medium for the isolation of Fg complex members. However, the production of pentachloronitrobenzene that is the most effective component of FG medium is discontinued and new media is required for the selective isolation of Fg complex members. In addition, the rapid diagnosis of isolated fungi is useful for the disease control. Novel tools have been developed for isolating and characterizing Fg complex members. FG21, a semi-selective medium for isolating Fg complex members, was developed using potato dextrose agar. Furthermore, a dipstick DNA chromatography assay was developed both to identify Fusarium graminearum sensu stricto and Fusarium asiaticum in the Fg complex and their trichothecene mycotoxin types. The easier isolation and characterization of Fg complex members in Japan was attained by the combined use of FG21 medium and the dipstick DNA chromatography assay.

Identification of a Novel ToxA Haplotype of Pyrenophora tritici-repentis from Japan.

Pyrenophora tritici-repentis was described first as a pathogen of wheat (tan spot) in Japan in the 1920s, but, since then, no reports on P. tritici-repentis race structure or its effectors in Japan have been published. In this study, 10 single-spore isolates of P. tritici-repentis were collected from bread wheat in Japan. These isolates were evaluated for virulence on four differential wheat genotypes and tested for the presence/absence of the effector-encoding genes, ToxA and ToxB, in multiplex PCR assays. These isolates were identified as ToxA producers, of which eight were designated as race 2 (ToxA producers) and two were classified as race 1 (ToxA and ToxC producers) based on their virulence patterns. Sequence analysis of the ToxA amplicons from these 10 isolates indicated the presence of a novel ToxA haplotype (denoted PtrA2). A comparative sequence analysis and resequencing of ToxA from reference P. tritici-repentis isolates showed that all previously published ToxA haplotypes in P. tritici-repentis were identical, and are hence denoted PtrA1 in this study. A total of 163 PtrToxA sequences from global origins were already deposited in GenBank and were confirmed identical to PtrA1. Sequence variation in PtrA1 and PtrA2 open reading frames were found at three positions: one synonymous mutation at position 412 (C/G) and two nonsynonymous mutations at positions 342 and 362 that alter amino acid sequence. These mutations did not seem to affect the necrosis development on a ToxA-sensitive wheat genotype when rated for symptoms 5 to 7 days after inoculation. This is the first report correctly confirming the presence of an additional novel ToxA haplotype in P. tritici-repentis for which we have predicted its isoform and updated the ToxA haplotype evolutionary network.

[Determination of Allyl Isothiocyanate in Mustard and Horseradish Extracts by Single Reference GC and HPLC Based on Relative Molar Sensitivities].

The main component of the Mustard and Horseradish extracts, which are used as natural food additives in Japan, is allyl isothiocyanate (AITC). The determination of AITC using GC-FID is the official method employed in the quality control assessments for these products. In this method, a commercially available AITC reagent is used as a calibrant. However, 1H-quantitative NMR (qNMR) analysis revealed that the AITC reagents contain impurity. Therefore, we examined the GC-FID and HPLC-refractive index detector (LC-RID) method based on relative molar sensitivities (RMSs) to high-purity single reference (SR). The RMSs of AITC/SR under the GC-FID and LC-RID conditions were accurately determined using qNMR. The AITC in two types of food additives was quantified using qNMR, SR GC-FID, and SR LC-RID methods. Both SR GC-FID and SR LC-RID showed good agreement within 2% with the AITC content determined by direct qNMR.

The utility of a deep learning-based algorithm for bone scintigraphy in patient with prostate cancer.

OBJECTIVE: Bone scintigraphy has often been used to evaluate bone metastases. Its functionality is evident in detecting bone metastasis in patients with malignant tumor including prostate cancer, as appropriate treatment and prognosis are dependent on the presence and degree of bone metastasis. The development of a deep learning-based algorithm in the field of information processing has been remarkable in recent years. We hypothesized that a deep learning-based algorithm is useful in diagnosing osseous metastases in patients with prostate cancer using bone scintigraphy. Thus, this study aims to examine the utility of deep learning-based algorithm in detecting bone metastases in patients with prostate cancer, as compared with nuclear medicine specialists. METHODS: In total, 139 serial patients with prostate cancer, who underwent whole-body bone scintigraphy, were enrolled in this study. Each scintigraphy examination was evaluated visually and independently by nuclear medicine specialists; this was also analyzed using a deep learning-based algorithm. The number of abnormal uptakes was assessed by the nuclear medicine specialists and with a software which used the deep learning-based algorithm, and the per-patient detection rate and the per-region detection rate were then calculated. The software automatically analyzed bone scintigraphy for the presence or absence of osseous metastasis in individual patients, for the 12 body regions. The detection rates analyzed separately by the nuclear medicine specialists and using the software were then compared. The sensitivity, specificity, and accuracy by the specialist and with the software were calculated. RESULTS: The sensitivity, specificity, and accuracy by the nuclear medicine specialists were 100%, 94.9% and 97.1%. On the other hand, they with the software were 91.7%, 87.3% and 89.2%. No statistically significant difference was determined between the per-patient detection rates assessed by the specialists versus the software. In regional assessment, there was also no statistically significant difference between most of the per-region detection rates (10 of 12 regions) by the specialists versus the results obtained by the software. CONCLUSIONS: The software with the deep learning-based algorithm might be used as diagnostic aid in the evaluation of bone metastases for prostate cancer patients.

Noninvasive estimation of quantitative myocardial blood flow with Tc-99m MIBI by a compartment model analysis in rat.

BACKGROUND: We aimed to investigate the use of dynamic cardiac planar images to estimate myocardial blood flow (MBF) by a compartment model analysis using time-to-peak (TP) map and compared it by the microsphere technique in rat. Positron emission tomography is considered the gold standard method, but is not available everywhere. By contrast, although myocardial perfusion imaging (MPI) with single-photon tracers is more widely available, it may be difficult to obtain adequate region of interest (ROI) settings. We proposed using the TP map to set the ROI, and hypothesized that this method could facilitate the measurement of absolute MBF by MPI in rat. METHODS: Twenty-one normal rats were studied. Dynamic planar images with Tc-99m MIBI were obtained, and input function and cardiac ROIs were set using the obtained TP map. MBF was estimated by a one-compartment model analysis with the Renkin-Crone model and by the microsphere technique. RESULTS: The MBFs from these two methods were significantly correlated. A negative proportional bias was observed, but no significant difference was observed between the mean MBFs calculated with each method. CONCLUSIONS: MBF estimation by a compartment model analysis using TP map could facilitate absolute MBF measurement in rats.

Determination of perillaldehyde in perilla herbs using relative molar sensitivity to single-reference diphenyl sulfone.

Perillaldehyde (PRL) is one of the essential oil components derived from perilla plants (Perilla frutescens Britton) and is a characteristic compound of the traditional medicine "perilla herb ()" listed in the The Japanese Pharmacopoeia, 17th edition (JP17). HPLC using an analytical standard of PRL has been used to quantitatively determine the PRL content in perilla herb. However, PRL reagents have been reported to decompose easily. In this study, we utilized an alternative quantitative method using on a single reference with relative molar sensitivity (RMS) based on the results of experiments performed in two laboratories. It was possible to calculate the exact RMS using an offline combination of 1H-quantitative NMR spectroscopy (1H-qNMR) and an HPLC/photodiode array (PDA) detector (or an HPLC/variable-wavelength detector [VWD]). Using the RMS of PRL to the single-reference compound diphenyl sulfone (DFS), which is an inexpensive and stable compound, the PRL content in the perilla herb could be determined using HPLC/PDA or HPLC/VWD without the need for the analytical standard of PRL. There was no significant difference between the PRL contents of perilla herb determined using the method employing the single-reference DFS with RMS and using the JP17 assay, the calibration curve of which was generated using the analytical standard of PRL with adjusted purity measured by 1H-qNMR. These results demonstrate that our proposed method using a single reference with RMS is suitable for quantitative assays of perilla herb and can be an alternative method for the current assay method defined in the JP17.

Rigorous monitoring of a large-scale marine stock enhancement program demonstrates the need for comprehensive management of fisheries and nursery habitat.

Release of captively-bred individuals into the wild is one of the most popular tools in fisheries, forestry, and wildlife management, and introgression of hatchery-reared animals into wild populations is of global concern. However, research and monitoring of impacts on wild populations are generally lacking, and the benefit of hatcheries for long-term fisheries and conservation goals is unclear. Using spatio-temporal genetic monitoring and a four-dacade time series of catch data, we quantified the effects on the size and genetic diversity of wild populations of one of the world's largest marine stock enhancement programs-the red sea bream (Pagrus major) in Kagoshima Bay, Japan. Our analyses found that the stock enhancement program reduced genetic diversity of the population, but the genetic effect diminished with increased size of the wild population. Increases to the seaweed communities and reduced fishing efforts were the primary factors associated with the wild population recovery; effects of aquaculture were much smaller. Our results represent crucial evidence that hatcheries for enhancement and conservation of populations cannot be successful over the long term unless sufficient efforts are also made to reduce harvest rates and rehabilitate natural habitats.

Relative molar sensitivities of carnosol and carnosic acid with respect to diphenylamine allow accurate quantification of antioxidants in rosemary extract.

We have been developing a high-performance liquid chromatography/photodiode array (HPLC/PDA) employing relative molar sensitivities (RMSs) and adopted it to the accurate quantification of carnosol (CL) and carnosic acid (CA) which are the antioxidants in rosemary extract. The method requires no references of CL or CA and instead uses RMSs with respect to diphenylamine (DPA) whose certified reference material is available from a reagent manufacturer. The molar and response ratios of the analytes to the reference in an artificial mixture of them were determined using 1H-quantitative nuclear magnetic resonance spectroscopy (1H-qNMR) and HPLC/PDA at a wavelength of 284 nm under isocratic condition, respectively, and then RMSs were calculated to be 0.111 for CL/DPA and 0.0809 for CA/DPA as averaged values in three HPLC-PDA instruments. The RMS values varied by up to 1.1% as relative standard deviation. To evaluate the performance of HPLC/PDA with the RMSs, the CL and CA contents in rosemary extracts were determined using DPA as a reference. The CL and CA contents were compared with those determined using calibration curves of CL and CA obtained by HPLC measurement of standard solutions prepared from their reagents whose absolute purities were determined using 1H-qNMR. The differences between the two methods for CL and CA were ≤3% as relative error. This chromatographic method with RMSs allows a simple and reliable quantification when reference of the analyte is unavailable.

Inter- and intra-observer reproducibility of quantitative analysis for FP-CIT SPECT in patients with DLB.

BACKGROUND: Dopamine transporter single photon emission CT (DAT-SPECT) is useful in the evaluation of dementia with Lewy bodies (DLB). The specific binding ratio (SBR) is an index to measure DAT density. However, poorly reproducible cases are occasionally experienced in clinical practice. We hypothesized that distance-weighted histogram (DWH) may be useful to improve the reproducibility of SBR. The purpose of this study was to investigate inter- and intra-observer reproducibility of SBR with conventional and DWH methods, and to visually evaluate the precision in reference voxel of interest (VOI) definition using these methods. METHODS: This study included 50 adult patients with probable DLB. They underwent brain MRI, DAT-SPECT, and cerebral blood flow SPECT with N-isopropyl-p-[123I]iodoamphetamine (I-123 IMP). SBR of the striatum was calculated using conventional and DWH method. For inter-observer reproducibility validation, conventional and DWH SBR were independently evaluated by experienced nuclear medicine physicians; these measurements were repeated by the nuclear medicine physician to investigate intra-observer reproducibility. RESULTS: Proper reference VOI definition was achieved in 60.0% using conventional SBR and in 98.0% with DWH SBR. Both conventional and DWH SBR demonstrated good inter- and intra-observer reproducibility, however, there were statistically significant inter- and intra-observer variations with conventional SBR measurements. Average inter- and intra-observer errors of conventional SBR were 7.9 and 6.1%, respectively. Conversely, DWH SBR errors were not observed in all patients. Moreover, average inter- and intra-observer errors were significantly higher in conventional SBR with improper reference VOI definition than in that with proper reference VOI definition. CONCLUSIONS: Although the reproducibility of conventional and DWH SBR was good, inter- and intra-observer bias could not be ignored in conventional SBR, particularly with improper reference VOI definition. Thus, DWH may be useful to improve inter- and intra-observer reproducibility of SBR.

SUV navigator enables rapid [18F]-FDG PET/CT image interpretation compared with 2D ROI and 3D VOI evaluations.

PURPOSE: Positron emission tomography (PET) and the maximum standardized uptake value (SUVmax) is a useful technique for assessing malignant tumors. Measurements of SUVmax in multiple lesions per patient frequently require many time-consuming procedures. To address this issue, we designed a novel interface named SUV Navigator (SUVnavi), and the purpose of this study was to investigate its utility. MATERIALS AND METHODS: We measured SUVmax in 661 lesions from 100 patients with malignant tumors. Diagnoses and SUVmax measurements were made with SUVnavi, 2D, and 3D measurements. SUV measurement accuracy in each method were also evaluated. RESULTS: The average reduction in time with SUVnavi versus 2D was 53.8% and 3D was 37.5%; time required with SUVnavi was significantly shorter than with 2D and 3D (P < 0.001 and P < 0.001, respectively). The time reduction and lesion number had a positive correlation (P < 0.001 and P < 0.001, respectively). SUVmax agreed with precise SUVmax in all lesions measured with SUVnavi and 3D but in only 466 of 661 lesions (70.5%) measured with 2D. CONCLUSION: SUVnavi may be useful for rapid [18F]-fluorodeoxyglucose positron emission tomography/computed tomography ([18F]-FDG PET/CT) image interpretation without reducing the accuracy of SUVmax measurement.

A novel iterative modified bicubic interpolation method enables high-contrast and high-resolution image generation for F-18 FDG-PET.

Positron emission tomography (PET) has become a useful and important technique in oncology. However, spatial resolution of PET is not high; therefore, small abnormalities can sometimes be overlooked with PET. To address this problem, we devised a novel algorithm, iterative modified bicubic interpolation method (IMBIM). IMBIM generates high resolution and -contrast image. The purpose of this study was to investigate the utility of IMBIM for clinical FDG positron emission tomography/X-ray computed tomography (PET/CT) imaging.We evaluated PET images from 1435 patients with malignant tumor and compared the contrast (uptake ratio of abnormal lesions to background) in high resolution image with the standard bicubic interpolation method (SBIM) and IMBIM. In addition to the contrast analysis, 340 out of 1435 patients were selected for visual evaluation by nuclear medicine physicians to investigate lesion detectability. Abnormal uptakes on the images were categorized as either absolutely abnormal or equivocal finding.The average of contrast with IMBIM was significantly higher than that with SBIM (P < .001). The improvements were prominent with large matrix sizes and small lesions. SBIM images showed abnormalities in 198 of 340 lesions (58.2%), while IMBIM indicated abnormalities in 312 (91.8%). There was statistically significant improvement in lesion detectability with IMBIM (P < .001).In conclusion, IMBIM generates high-resolution images with improved contrast and, therefore, may facilitate more accurate diagnoses in clinical practice.

Asteltoxins from the Entomopathogenic Fungus Pochonia bulbillosa 8-H-28.

New asteltoxins C (3) and D (4) were found in the extract of the entomopathogenic fungus Pochonia bulbillosa 8-H-28. Compound 2, which was spectroscopically identical with the known asteltoxin B, was isolated, and structural analysis led to a revision of the structure of asteltoxin B. Compounds 2 and 4 have a novel tricyclic ring system connected to a dienyl α-pyrone structure. Compound 3 has a 2,8-dioxabicyclo[3.3.0]octane ring similar to that of asteltoxin (1). Compound 3 showed potent antiproliferative activity against NIAS-SL64 cells derived from the fat body of Spodoptera litura larvae, while 2 and 4 were inactive.

A new cell line from the fat body of Spodoptera litura (Lepidoptera, Noctuidae) and detection of lysozyme activity release upon immune stimulation.

A new cell line, designated NIAS-SL64, was established from the fat body of the fifth instar larvae of the common cutworm Spodoptera litura. NIAS-SL64 cells grew as spindle-shaped and non-adherent cells in the insect-specific cell culture medium MGM-450 supplemented with 10% fetal bovine serum. Criterions for the establishment of the NIAS-SL64 cell line is spindle shape and length (30~90 µm) stabilized after 100 passages. The doubling time of the cells was 24 h at 25°C. Lipopolysaccharide significantly stimulated the release of lysozyme activity by NIAS-SL64 cells. Lysozyme is one of the components of the innate immunity and plays important role as lytic enzyme in infection. Lysozyme activity released from NIAS-SL64 would be a marker for immune response. The released lysozyme activity critically depends on morphology of the cells and would be a criterion of the establishment of the cell line. Lysozyme activity was suppressed in a dose-dependent manner by the immunosuppressive agent cyclosporin A.