[Effect of Training Data Differences on Accuracy in MR Image Generation Using Pix2pix].

PURPOSE: Using a magnetic resonance (MR) image generation technique with deep learning, we elucidated whether changing the training data patterns affected image generation accuracy. METHODS: The pix2pix training model generated T1-weighted images from T2-weighted images or FLAIR images. Head MR images obtained at our hospital were used in this study. We prepared 300 cases for each model and four training data patterns for each model (a: 150 cases for one MR system, b: 300 cases for one MR system, c: 150 cases and augmentation data for one MR system, and d: 300 cases for two MR systems). The extension data were images of 150 cases rotated in the XY plane. The similarity between the images generated by the training and evaluation data in each group was evaluated using the peak signal-to-noise ratio (PSNR) and structural similarity (SSIM). RESULTS: For both MR systems, the PSNR and SSIM were higher for training dataset b than training dataset a. The PSNR and SSIM were lower for training dataset d. CONCLUSION: MR image generation accuracy varied among training data patterns.

Morphology Observation of Two-Dimensional Monolayers of Model Proteins on Water Surface as Revealed by Dropping Method.

We have investigated the morphology of two-dimensional monolayers of gramicidin-D (GD) and alamethicin (Al) formed on the water surface by the dropping method (DM) using surface tension measurement (STm), Brewster angle microscopy (BAM), and atomic force microscopy (AFM). Dynamic light scattering (DLS) revealed that GD in alcoholic solutions formed a dimeric helical structure. According to the CD and NMR spectroscopies, GD molecules existed in dimer form in methanol and lipid membrane environments. The STm results and BAM images revealed that the GD dimer monolayer was in a liquid expanded (LE) state, whereas the Al monolayer was in a liquid condensed (LC) state. The limiting molecular area (A0) was 6.2 ± 0.5 nm2 for the GD-dimer and 3.6 ± 0.5 nm2 for the Al molecule. The AFM images also showed that the molecular long axes of both the GD-dimer and Al were horizontal to the water surface. The stability of each monolayer was confirmed by the time dependence of the surface pressure (π) observed using the STm method. The DM monolayer preparation method for GD-dimer and Al peptide molecules is a useful technique for revealing how the model biological membrane's components assemble in two dimensions on the water surface.

The Interaction between Anesthetic Isoflurane and Model-Biomembrane Monolayer Using Simultaneous Quartz Crystal Microbalance (QCM) and Quartz Crystal Impedance (QCI) Methods.

The interaction between anesthetic Isoflurane (Iso) and model-biomembrane on the water surface has been investigated using quartz crystal microbalance (QCM) and quartz crystal impedance (QCI) methods. The model-biomembranes used were dipalmitoyl phosphatidyl choline (DPPC), DPPC-palmitic acid (PA) mixture (DPPC:PA = 8:2), DPPC-Alamethicin (Al) mixture (DPPC:Al = 39:1), and DPPC-ß-Lactoglobulin (ßLG) mixture (DPPC:ßLG = 139:1) monolayers, respectively. The quartz crystal oscillator (QCO) was attached horizontally to each monolayer, and QCM and QCI measurements were performed simultaneously. It was found that Iso hydrate physisorbed on each monolayer/water interface from QCM and changed those interfacial viscosities from QCI. With an increase in Iso concentration, pure DPPC, DPPC-PA mixed, and DPPC-Al mixed monolayers showed a two-step process of Iso hydrate on both physisorption and viscosity, whereas it was a one-step for the DPPC-ßLG mixed monolayer. The viscosity change in the DPPC-ßLG mixed monolayer with the physisorption of Iso hydrate was much larger than that of other monolayers, in spite of the one-step process. From these results, the action mechanism of anesthetics and their relevance to the expression of anesthesia were discussed, based on the "release of interfacial hydrated water" hypothesis on the membrane/water interface.

Design of Cell-Adhesive Shellac Derivatives and Endowment of Photoswitchable Cell-Adhesion Properties.

The emergence of new biodegradable cell-adhesion materials is an attractive topic in biomaterial chemistry, particularly for the development of cell incubation scaffolds and drug encapsulation materials used in in situ regenerative therapy. Shellac is a natural resin with unique film-forming properties and high miscibility with various chemicals, in addition to being biodegradable and nontoxic to biological systems. However, since native shellac does not adhere to mammalian cells, there have been no reports of using shellac to develop cell-adhesive biomaterials. In this study, we report on the development of cell-adhesive shellac derivatives through slight chemical modification. Shellac is a mixture of oligoesters that consists of hydroxyl fatty acids and resin acids, and therefore, all oligomers have one carboxylic acid group at the terminal. We discovered that a simple modification of hydrophobic chemical groups, particularly those containing aromatic groups in the ester form, could dramatically improve cell-adhesion properties for mammalian cells. Furthermore, by using photocleavable esters containing aromatic groups, we successfully endowed photoswitchable properties in cell adhesion. Given that shellac is a low-cost, biodegradable, and nontoxic natural resin, the modified shellacs have the potential to become new and attractive biomaterials applicable to in situ regenerative therapy.

Small Dense Low-Density Lipoprotein Cholesterol Levels in Breakfast Skippers and Staple Foods Skippers.

AIMS: Skipping breakfast is known as a cardiovascular disease (CVD) risk. Recently, eating and dietary patterns have been varied in many countries, however, the mechanisms of promoting CVD are still unclear. Our goal was to assess the effects of eating and dietary patterns on CVD risk factors, with a focus on lipid parameters including serum concentration of small dense low-density lipoprotein cholesterol (sdLDL-C). METHODS: Subjects consisted of 27,997 Japanese men and women, who had medical check-up. Lipid parameters including sdLDL-C levels in breakfast skippers were compared with those in breakfast eaters. Lipid parameters in staple foods skippers were also compared with those in staple foods eaters. RESULTS: Breakfast skippers had significantly (p＜0.01) higher serum levels of median sdLDL-C than breakfast eaters in both genders (34.7 versus 32.0 mg/dL in men, 25.4 versus 24.9 mg/dL in women, respectively), and the same was true for sdLDL-C/LDL-C ratio (0.276 versus 0.260 in men, 0.218 versus 0.209 in women, respectively). Similarly, staple foods skippers had significantly higher sdLDL-C level than staple foods eaters in both genders (34.1 versus 31.6 mg/dL in men, 25.8 versus 24.7 mg/dL in women), and the same went for sdLDL-C/LDL-C ratio (0.278 versus 0.256 in men, 0.215 versus 0.208 mg/dL in women, respectively). CONCLUSION: Our data indicate that both skipping breakfast and having meals without staple foods increase serum sdLDL-C concentration and cause unfavorable lipid profiles, and then may promote CVD. These finding provide evidence for the importance of having breakfast and meals with staple foods for preventing CVD.

Highly efficient catalytic production of oximes from ketones using in situ-generated H2O2.

The ammoximation of cyclohexanone using preformed hydrogen peroxide (H2O2) is currently applied commercially to produce cyclohexanone oxime, an important feedstock in nylon-6 production. We demonstrate that by using supported gold-palladium (AuPd) alloyed nanoparticles in conjunction with a titanium silicate-1 (TS-1) catalyst, H2O2 can be generated in situ as needed, producing cyclohexanone oxime with >95% selectivity, comparable to the current industrial route. The ammoximation of several additional simple ketones is also demonstrated. Our approach eliminates the need to transport and store highly concentrated, stabilized H2O2, potentially achieving substantial environmental and economic savings. This approach could form the basis of an alternative route to numerous chemical transformations that are currently dependent on a combination of preformed H2O2 and TS-1, while allowing for considerable process intensification.

Reference interval for serum concentration of small dense low-density lipoprotein cholesterol in the healthy Japanese population.

BACKGROUND: Small dense low-density lipoprotein a smaller and denser subfraction among whole low density lipoprotein particles is known to be highly atherogenic. The reference interval (RI) is not strictly defined for serum concentration of sdLDL-cholesterol (sdLDL-C) in Japan. The purpose of this study is to set the reference interval for sdLDL-C in healthy subjects. METHODS: The population of this cross-sectional study was consisted of 40,862 individuals who had annual health checkups, and healthy subjects were extracted based on exclusion criteria such as medical history, social history, and blood sampling test results. Their serum sdLDL-C values were statistically analyzed and the RIs were set in men, premenopausal women, and postmenopausal women separately. RESULTS: The mean values of serum sdLDL-C in healthy subjects were 23.9 mg/dL in men, 20.0 mg/dL in premenopausal women and 23.7 mg/dL in postmenopausal women, and the RIs were 12.6-45.3 mg/dL in men, 11.4-35.1 mg/dL in premenopausal women and 14.6-38.6 mg/dL in postmenopausal women. Serum sdLDL-C values were significantly higher in men than in women. Besides, sdLDL-C values were significantly higher in postmenopausal women than in premenopausal women. In both genders, sdLDL-C values tended to increase with age. CONCLUSION: These results suggest that the RIs for sdLDL-C are recommended as follows: 13-45 mg/dL in men, 11-35 mg/dL in premenopausal women, and 15-39 mg/dL in postmenopausal women, respectively. Aside from these RIs, it is also necessary to define clinical cutoff values graded according to individual risk levels for atherosclerotic cardiovascular diseases.

[Accuracy of Classification of Cerebral Blood Flow Reduction Patterns Using Statistical Analysis Images Generated with Simulated SPECT Datasets via Deep Learning].

PURPOSE: The aim of this study was to evaluate the classification accuracy of specific blood flow reduction patterns in clinical images by deep learning using simulation data. METHODS: We obtained Z-score maps for 100 cases each of simulated Alzheimer's disease (AD), simulated dementia with Lewy bodies (DLB), and simulated normal cognition (NC) by performing statistical analysis of the simulation data that provided defects and healthy patient data. The clinical images were determined by reference to radiological reports, and Z-score maps of AD (n=33), DLB (n=20), and NC (n=28) were used. A network was constructed with reference to AlexNet, 4-fold cross-validation was performed using only simulation data, and classification accuracy was evaluated. We also trained the model using the simulation data and classified the clinical images. RESULTS: The accuracy rate of classification between simulations was 96.2% and that of the clinical images was 84.2%. CONCLUSION: Through deep learning using simulation data, clinical images may be classified with an accuracy of 84.2%.

Relationships between Smoking Status, Cardiovascular Risk Factors, and Lipoproteins in a Large Japanese Population.

AIMS: Smoking is a major risk factor for cardiovascular disease (CVD), a leading cause of death and disability. Other CVD risk factors include age, gender, hypertension, diabetes, increased low-density lipoprotein cholesterol (LDL-C) and decreased high-density lipoprotein cholesterol (HDL-C). Our goal was to assess relationships between smoking status and CVD risk factors, with a focus on direct LDL-C, HDL-C, triglycerides (TG) and small dense LDL-C (sdLDL-C). METHODS: A total of 34,497 Japanese men and women, mean age 51 years, had their CVD risk factors including fasting serum total cholesterol, TG, HDL-C, sdLDL-C, and direct LDL-C assessed. One-way ANOVA and multiple linear regression analyses were carried to assess the interrelationships of these parameters with smoking. RESULTS: In both men and women, current smokers had significantly (p＜0.001) higher median TG (+19.6%, +16.9%) and sdLDL-C levels (+12.7%, +4.2%) levels, and significantly (p＜0.001) lower HDL-C levels (-7.3%, -4.3%) than non-smokers. They were also significantly (p＜0.05) more likely to have TG values ＞150 mg/dL (+56.8%, +116.3%), sdLDL-C ＞40.1 mg/dL (+28.8%, +44.9%), and HDL-C ＜40 mg/dL (+89.8%, +114.3%). Ex-smokers generally had lipid values that were intermediate between non-smokers and current smokers. Multivariate analysis confirmed the significance of these relationships. CONCLUSION: Our data indicate that current cigarette smoking is associated with increased TG and sdLDL-C levels, as well as decreased HDL-C levels. Furthermore, smoking effect on lipid profiles remain after cessation. These data provide further justification for smoking cessation.

Acute eosinophilic pneumonia following inhalation of turpentine oil: A case report.

Acute eosinophilic pneumonia (AEP) is an eosinophilic lung disease associated with environmental substances including smoking. Although the etiology of AEP has not been fully elucidated, it has been hypothesized that IL-33 plays a central role in the pathogenesis of AEP. Turpentine oil, from resins of pine trees, is not only used in paints, but also utilized in experimental animal models of inflammation because it leads to the production of inflammatory cytokines including IL-33. Here, we report the first case of AEP following turpentine oil inhalation. A 67-year-old woman reported using urushiol with turpentine oil to repair home goods. She had fever and persistent cough after turpentine inhalation over a very short period of time. The chest X-ray image showed consolidation in the upper right lung field. Laboratory findings indicated that there was no evidence of infection, collagen vascular diseases, and other allergic diseases that cause pneumonia, but analysis of the bronchoalveolar lavage fluid revealed 29% eosinophils with a small number of lipid-laden macrophages. With these findings, the diagnostic criteria of AEP was met. We rendered a diagnosis of AEP by inhalation of turpentine because no other cause for AEP was identified even with a structured questionnaire survey. The manifestations resolved immediately after steroid therapy. This is the first report of a case of AEP caused by the inhalation of turpentine oil.

Effect of Escherichia coli on phospholipid monolayers: surface tensiometry and Brewster angle microscopy measurements.

The effect of Escherichia coli (E. coli) cells on two phospholipids [dipalmitoyl phosphatidylcholine (DPPC) and dimyristoyl phosphatidylcholine (DMPC)] monolayers at the surface of a 1.5 wt% NaCl salt solution has been investigated using surface tension measurement and Brewster angle microscopy. The results showed that a DPPC monolayer that has an elastic structure was changed in morphology by interaction with E. coli cells, whereas a DMPC monolayer that has an expandable structure did not change in morphology. In particular, the morphology changed significantly around the liquid-expanded (LE)-liquid-condensed (LC) phase transition point for the DPPC monolayer. It was found that the LE-LC phase transition range in a DPPC monolayer was sensitive to influence from the outside of the monolayer such as the action of E. coli cells. Such a monolayer has the potential for application as a membrane sensor for detecting a small amount of bacteria in a short time.

Neuromyelitis optica spectrum disorder secondary to treatment with anti-PD-1 antibody nivolumab: the first report.

BACKGROUND: Immune checkpoint blockade is developed as standard treatment for non-small cell lung cancer. However immune-related adverse events (irAE) have still unknown complications. Here, we report a patient with lung squamous cell carcinoma who developed neuromyelitis optica spectrum disorder with nivolumab. CASE PRESENTATION: A 75-year-old Japanese man with lung squamous cell carcinoma was administered nivolumab as second-line treatment. Two months after treatment with nivolumab, he presented acute paralysis in the bilateral lower limbs, sensory loss. Spinal magnetic resonance imaging showed T2 hyperintense lesions between C5-6 and Th12-L1. He was diagnosed with neuromyelitis optica spectrum disorder (NMOSD) by anti-aquaporin-4 antibody-positive in the serum and other examinations. After treatment, steroid reactivity was poor. CONCLUSION: This is the first patient who developed anti-AQP4 antibody-positive NMOSD as a nivolumab-induced irAE. Clinicians should be aware of this kind of potential neurological complication by using immune check point inhibitor and start the treatment of this irAE as soon as possible.

Influence of Attenuation Correction by Brain Perfusion SPECT/CT Using a Simulated Abnormal Bone Structure: Comparison Between Chang and CT Methods.

Brain perfusion SPECT has physical phenomena such as attenuation, scatter, and degradation of resolution that impair accuracy on data acquisition. Chang and CT methods have spread application for attenuation correction (AC) and indicate the utility of AC using a brain phantom without a bone or with a normal bone structure. However, nonuniform AC of an abnormal bone structure such as postoperative bone defect after burr-hole surgery has not yet been evaluated. Therefore, we evaluated the influence of nonuniform AC of an abnormal bone structure between the 2 AC methods. Methods: We created 5 brain phantoms simulating an abnormal bone structure such as frontal, occipital, and right temporal bone defects as well as with and without a bone, which compared the influence among 3-dimensional ordered-subset expectation maximization (OSEM) incorporating scatter, attenuation, and resolution recovery corrections, and obtained 3 reconstruction processing images: OSEM (non-AC; NAC), OSEM (Chang), and OSEM (CTAC). The average counts of the 5 brain phantoms by OSEM (NAC), OSEM (Chang), and OSEM (CTAC) were evaluated by a count profile curve and counts ratio in the region of interest. Results: The counts of OSEM (NAC) and OSEM (Chang) with a bone were approximately 7% higher than those without a bone, whereas OSEM (CTAC) had a similar count ratio. The count ratio of frontal or occipital lobes with a bone defect on both OSEM (NAC) and OSEM (Chang) was 5%-10% higher than that in frontal or occipital lobes without a bone defect; however, OSEM (CTAC) had nearly identical frontal or occipital lobes with and without a bone defect. Conclusion: We conducted a phantom study simulated with and without a bone defect to demonstrate the influence of brain counts between 2 different AC methods. Although the Chang method did not correct the influence of the bone defect due to the use of a uniform attenuation coefficient, the CTAC method correctly conducted AC regardless of the presence of a bone defect.

Effect of resolution recovery using graph plots on regional cerebral blood flow in healthy volunteers.

PURPOSE: We evaluated the effect of resolution recovery (RR) using graph plots on regional cerebral blood flow (rCBF) in brain perfusion single-photon emission computed tomography (SPECT) images derived from healthy volunteers and patients diagnosed with probable Alzheimer's disease. METHOD: We acquired brain perfusion SPECT images with scatter correction (SC), computed tomography-based attenuation correction (CTAC), and RR from a three-dimensional brain phantom and from healthy volunteers. We then compared contrast-to-noise ratio, count density ratios, increase maps, and rCBF using statistical parametric mapping 8. RESULTS: Regional brain counts were significantly increased from 20-24% with SC, CTAC, and RR compared with SC and CTAC. Mean CBF in healthy volunteers was 42.5 ± 5.4 mL/100 g/min. Average rCBF determined using SC, CTAC and RR increased 7.5, 2.0, and 3.7% at the thalamus, posterior cingulate, and whole brain, respectively, compared with SC and CTAC. CONCLUSION: Resolution recovery caused variations in normal rCBF because counts increased in cerebral regions.

Can a Resting-State Functional Connectivity Index Identify Patients with Alzheimer's Disease and Mild Cognitive Impairment Across Multiple Sites?

Resting-state functional connectivity is one promising biomarker for Alzheimer's disease (AD) and mild cognitive impairment (MCI). However, it is still not known how accurately network analysis identifies AD and MCI across multiple sites. In this study, we examined whether resting-state functional connectivity data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) could identify patients with AD and MCI at our site. We implemented an index based on the functional connectivity frequency distribution and compared performance for AD and MCI identification with multivoxel pattern analysis. The multivoxel pattern analysis using a connectivity map of the default mode network showed good performance, with an accuracy of 81.9% for AD and MCI identification within the ADNI, but the classification model obtained from the ADNI failed to classify AD, MCI, and healthy elderly adults from our site, with an accuracy of only 43.1%. In contrast, a functional connectivity index of the medial temporal lobe based on the frequency distribution showed moderate performance, with an accuracy of 76.5-80.3% for AD identification within the ADNI. The performance of this index was similar for our data, with an accuracy of 73.9-82.6%. The frequency distribution-based index of functional connectivity could be a good biomarker for AD across multiple sites.

Use of a digital phantom developed by QIBA for harmonizing SUVs obtained from the state-of-the-art SPECT/CT systems: a multicenter study.

BACKGROUND: Although quantitative analysis using standardized uptake value (SUV) becomes realistic in clinical single-photon emission computed tomography/computed tomography (SPECT/CT) imaging, reconstruction parameter settings can deliver different quantitative results among different SPECT/CT systems. This study aims to propose a use of the digital reference object (DRO), which is a National Electrical Manufacturers Association (NEMA) phantom-like object developed by the Quantitative Imaging Biomarker Alliance (QIBA) fluorodeoxyglucose-positron emission tomography technical committee, for the purpose of harmonizing SUVs in Tc-99m SPECT/CT imaging. METHODS: The NEMA body phantom with determined Tc-99m concentration was scanned with the four state-of-the-art SPECT/CT systems. SPECT data were reconstructed using different numbers of the product of subset and iteration numbers (SI) and the width of 3D Gaussian filter (3DGF). The mean (SUVmean), maximal (SUVmax), and peak (SUVpeak) SUVs for six hot spheres (10, 13, 17, 22, 28, and 37 mm) were measured after converting SPECT count into SUV using Becquerel calibration factor. DRO smoothed by 3DGF with a FWHM of 17 mm (DRO17 mm) was generated, and the corresponding SUVs were measured. The reconstruction condition to yield the lowest root mean square error (RMSE) of SUVmeans for all the spheres between DRO17 mm and actual phantom images was determined as the harmonized condition for each SPECT/CT scanner. Then, inter-scanner variability in all quantitative metrics was measured before (i.e., according to the manufacturers' recommendation or the policies of their own departments) and after harmonization. RESULTS: RMSE was lowest in the following reconstruction conditions: SI of 100 and 3DGF of 13 mm for Brightview XCT, SI of 160 and 3DGF of 3 pixels for Discovery NM/CT, SI of 60 and 3DGF of 2 pixels for Infinia, and SI of 140 and 3DGF of 15 mm for Symbia. In pre-harmonized conditions, coefficient of variations (COVs) among the SPECT/CT systems were greater than 10% for all quantitative metrics in three of the spheres, SUVmax and SUVmean, in one of the spheres. In contrast, all metrics except SUVmax in the 17-mm sphere yielded less than 10% of COVs after harmonization. CONCLUSIONS: Our proposed method clearly reduced inter-scanner variability in SUVs. A digital phantom developed by QIBA would be useful for harmonizing SUVs in multicenter trials using SPECT/CT.

Observation of Zn-photoprotoporphyrin red Autofluorescence in human bronchial cancer using color-fluorescence endoscopy.

BACKGROUND: We observed red autofluorescence emanating from bronchial cancer lesions using a sensitive color-fluorescence endoscopy system. We investigated to clarify the origin of the red autofluorescence. METHODS: The wavelengths of the red autofluorescence emanating from lesions were measured in eight patients using a spectrum analyzer and compared based on pathologic findings. Red autofluorescence at 617.3, 617.4, 619.0, and 617.1 nm was emitted by normal bronchus, inflamed tissue, tissue exhibiting mild dysplasia, and malignant lesions, respectively. Protoporphyrin, uroporphyrin, and coproporphyrin, the major porphyrin derivatives in human blood, were purchased to determine which porphyrin derivative is the source of red fluorescence when acquired de novo. We synthesized photoporphyrin, Zn-protoporphyrin and Zn-photoprotoporphyrin from protoporphyrin. RESULTS: Coproporphyrin and uroporphyrin emitted only weak fluorescence. Fluorescence was emitted by our synthesized Zn-photoprotoporphyrin at 625.5 nm and by photoprotoporphyrin at 664.0 nm. CONCLUSIONS: From these results, we conclude that Zn-photoprotoporphyrin was the source of the red autofluorescence observed in bronchial lesions. Zn-protoporphyrin is converted to Zn-photoprotoporphyrin by radiation with excitation light. Our results suggest that red autofluorescence emanating from Zn-photoprotoporphyrin in human tissues could interfere with photodynamic diagnosis using porphyrin derivatives such as Photofrin® and Lazerphyrin® with a sensitive endoscopy system, because color cameras cannot differentiate Zn-photoprotoporphyrin red fluorescence from that of other porphyrin derivatives.

Does applying resolution recovery to normal databases confer an advantage over conventional 3D-stereotactic surface projection techniques?

We evaluated a novel normal database (NDB) generated using single photon emission computed tomography (SPECT) data obtained from healthy brains by using a SPECT/CT system, analyzed using a resolution recovery (RR) technique applied to the three-dimensional stereotactic surface projection (3D-SSP) technique. We used a three-dimensional ordered subset expectation maximization method (3D-OSEM) with applied scatter correction (SC), attenuation correction, and RR to reconstruct the data. We verified the accuracy of the novel NDB's values (Z, extent, and error scores), and compared the novel NDB to the 3D-SSP technique by using simulated misery perfusion-related patient data from a conventional NDB. In addition, Z, extent, and error scores at the precuneus, cuneus, and posterior cingulate were compared under different reconstruction conditions by using the patient data. In the simulation, Z scores decreased when using the novel NDB corrected using computed tomography-based attenuation correction (CTAC), SC, and RR. The extent scores of the posterior cingulate increased using the novel NDB, relative to the other NDBs. The error score with the novel NDB without RR decreased by 15% compared to that of the conventional NDB. Z scores generated from patient data decreased in the novel NDB with RR. The extent scores tended to decrease in the novel NDB with RR. The extent scores in the novel NDB with RR improved at the posterior cingulate, compared to the scores with the other NDBs. However, applying RR to the novel NDB conferred no advantage because the cut-off of the current Z score must be reconsidered when using the additive RR technique.