[Segmentation of Mass in Mammogram Using Gaze Search Patterns].

PURPOSE: It is very difficult for a radiologist to correctly detect small lesions and lesions hidden on dense breast tissue on a mammogram. Therefore, recently, computer-aided detection (CAD) systems have been widely used to assist radiologists in interpreting images. Thus, in this study, we aimed to segment mass on the mammogram with high accuracy by using focus images obtained from an eye-tracking device. METHODS: We obtained focus images for two mammography expert radiologists and 19 mammography technologists on 8 abnormal and 8 normal mammograms published by the DDSM. Next, the auto-encoder, Pix2Pix, and UNIT learned the relationship between the actual mammogram and the focus image, and generated the focus image for the unknown mammogram. Finally, we segmented regions of mass on mammogram using the U-Net for each focus image generated by the auto-encoder, Pix2Pix, and UNIT. RESULTS: The dice coefficient in the UNIT was 0.64±0.14. The dice coefficient in the UNIT was higher than that in the auto-encoder and Pix2Pix, and there was a statistically significant difference (p<0.05). The dice coefficient of the proposed method, which combines the focus images generated by the UNIT and the original mammogram, was 0.66±0.15, which is equivalent to the method using the original mammogram. CONCLUSION: In the future, it will be necessary to increase the number of cases and further improve the segmentation.

Hyporesponsiveness to erythropoiesis-stimulating agent in non-dialysis-dependent CKD patients: The BRIGHTEN study.

Among non-dialysis-dependent chronic kidney disease (ND-CKD) patients, a low hematopoietic response to erythropoiesis-stimulating agents (ESAs) is a predictor for poor renal and cardiovascular outcome. To assess the method for evaluating hyporesponsiveness to ESA in patients with ND-CKD, a multicenter, prospective, observational study of 1,980 adult patients with ND-CKD with renal anemia was conducted. Darbepoetin alfa (DA) and iron supplement administrations were provided according to the recommendation of the attached document and the guidelines of JSDT (Japanese Society of Dialysis and Transplantation). The primary outcomes were progression of renal dysfunction and major adverse cardiovascular events. ESA responsiveness was assessed using pre-defined candidate formulae. During the mean follow-up period of 96 weeks, renal and cardiovascular disease (CVD) events occurred in 683 (39.6%) and 174 (10.1%) of 1,724 patients, respectively. Among pre-set candidate formulae, the one expressed by dividing the dose of DA by Hb level at the 12-week DA treatment was statistically significant in predicting renal (hazard ratio [HR], 1.449; 95% confidence interval [CI], 1.231-1.705; P<0.0001) and CVD events (HR, 1.719; 95% CI, 1.239-2.386; P = 0.0010). The optimum cut-off values for both events were close to 5.2. In conclusion, hyporesponsiveness to ESA in ND-CKD cases, which is associated with a risk for renal and CVD events, may be evaluated practicably as the dose of DA divided by the Hb level at the 12-week DA treatment, and the cut-off value of this index is 5.2. A search for the causes of poor response and measures for them should be recommended in such patients. Trial registration: ClinicalTrials. gov Identifier: NCT02136563; UMIN Clinical Trial Registry Identifier: UMIN000013464.

Absence of diffusion-weighted imaging abnormalities in a patient with neuronal intranuclear inclusion disease.

INTRODUCTION: Herein, we report a genetically confirmed case of neuronal intranuclear inclusion disease without characteristic subcortical hyperintensities on diffusion-weighted imaging. CASE PRESENTATION: A 75-year-old man was admitted to our hospital with subacute onset of conscious disturbance. Except for gastric cancer, he had no apparent past medical or family history. He presented with transient fever, vomiting, and urinary retention. On admission, no apparent abnormal intensity was detected on diffusion-weighted imaging. The symptoms improved within 10 days, without any medical treatment. Additional inspections were performed under suspicion of neuronal intranuclear inclusion disease. Intranuclear inclusions were found not only from skin biopsy but also from his stomach specimens, which had been resected 6 years previously. Subsequent genetic testing revealed repeat expansion of GGC amplification in NOTCH2NLC. CONCLUSION: Characteristic neuroimaging and skin biopsy findings are important clues for diagnosing neuronal intranuclear inclusion diseases. Nonetheless, confirming a diagnosis is difficult due to the diversity of clinical manifestations and radiological features. Clinicians should suspect neuronal intranuclear inclusion disease in patients with transient encephalitic episodes, even if no abnormalities are detected on diffusion-weighted imaging.

Podocyte-specific deletion of tubular sclerosis complex 2 promotes focal segmental glomerulosclerosis and progressive renal failure.

Obesity can initiate and accelerate the progression of kidney diseases. However, it remains unclear how obesity affects renal dysfunction. Here, we show that a newly generated podocyte-specific tubular sclerosis complex 2 (Tsc2) knockout mouse model (Tsc2Δpodocyte) develops proteinuria and dies due to end-stage renal dysfunction by 10 weeks of age. Tsc2Δpodocyte mice exhibit an increased glomerular size and focal segmental glomerulosclerosis, including podocyte foot process effacement, mesangial sclerosis and proteinaceous casts. Podocytes isolated from Tsc2Δpodocyte mice show nuclear factor, erythroid derived 2, like 2-mediated increased oxidative stress response on microarray analysis and their autophagic activity is lowered through the mammalian target of rapamycin (mTOR)-unc-51-like kinase 1 pathway. Rapamycin attenuated podocyte dysfunction and extends survival in Tsc2Δpodocyte mice. Additionally, mTOR complex 1 (mTORC1) activity is increased in podocytes of renal biopsy specimens obtained from obese patients with chronic kidney disease. Our work shows that mTORC1 hyperactivation in podocytes leads to severe renal dysfunction and that inhibition of mTORC1 activity in podocytes could be a key therapeutic target for obesity-related kidney diseases.

[Multiple mononeuropathy associated with systemic sclerosis with vasculitis confirmed by nerve biopsy: a case report].

A 68-year-old woman with a medical history of interstitial pneumonia associated with systemic sclerosis (SSc) presented with numbness of the lower limbs and left drop foot. She was diagnosed with multiple mononeuropathy based on the laterality of her symptoms, muscle weakness, thermal hypoalgesia, and nerve conduction study findings. Left sural nerve biopsy showed vasculitis, and steroid therapy was effective. This case highlights the importance of histopathological assessment to select an appropriate treatment strategy.

The rice ethylene response factor OsERF83 positively regulates disease resistance to Magnaporthe oryzae.

Rice blast caused by Magnaporthe oryzae is one of the most destructive diseases of rice (Oryza sativa) worldwide. Here, we report the identification and functional characterization of a novel ethylene response factor (ERF) gene, OsERF83, which was expressed in rice leaves in response to rice blast fungus infection. OsERF83 expression was also induced by treatments with methyl jasmonate, ethephon, and salicylic acid, indicating that multiple phytohormones could be involved in the regulation of OsERF83 expression under biotic stress. Subcellular localization and transactivation analyses demonstrated that OsERF83 is a nucleus-localized transcriptional activator. A gel-shift assay using recombinant OsERF83 protein indicated that, like other ERFs, it binds to the GCC box. Transgenic rice plants overexpressing OsERF83 exhibited significantly suppressed lesion formation after rice blast infection, indicating that OsERF83 positively regulates disease resistance in rice. Genes encoding several classes of pathogenesis-related (PR) proteins, including PR1, PR2, PR3, PR5, and PR10, were upregulated in the OsERF83ox plants. Taken together, our findings show that OsERF83 is a novel ERF transcription factor that confers blast resistance by regulating the expression of defense-related genes in rice.

[Atypical hemolytic uremic syndrome in an elderly patient successfully treated with eculizumab].

Herein, we present an elderly onset case of aHUS successfully treated with eculizumab. An 80-year-old woman with severe anemia, thrombocytopenia, and acute renal dysfunction was admitted to our hospital. A laboratory test revealed steep elevation in the LDH level, and the peripheral blood smear showed erythrocyte fragmentations. Accordingly, we diagnosed thrombotic microangiopathy, and treatment with plasma exchange was immediately initiated. In addition, she required hemodialysis because of rapid impairment of the renal function. After excluding Shiga toxin-producing Escherichia coli infection and malignancy and confirming her ADMTS13 activity above 10%, we diagnosed aHUS, according to the Japanese diagnostic criteria for aHUS. Next, we initiated treatment with eculizumab. Her hematological findings improved 23 days after the starting of eculizumab. In addition, her renal function gradually recovered, and hemodialysis was discontinued. The genetic test for several complement regulatory genes tested negative. The onset of aHUS is reported in children or young adults and is rarely reported in elderly. However, our case suggests the importance of precisely diagnosing aHUS and initiating early administration of eculizumab for improving the outcome even in elderly patients.

Rationale and design of oBservational clinical Research In chronic kidney disease patients with renal anemia: renal proGnosis in patients with Hyporesponsive anemia To Erythropoiesis-stimulating agents, darbepoetiN alfa (BRIGHTEN Trial).

BACKGROUND: Renal anemia is an important complication in non-dialysis chronic kidney disease (CKD) patients as well as in dialysis patients. Although recombinant human erythropoietin has dramatically improved prognosis and quality of life in these patients, there have been issues among non-dialysis CKD patients who exhibit hyporesponsiveness to erythropoiesis-stimulating agent (ESA). The causes and definition of ESA hyporesponsiveness, as well as the incidence of renal and cardiovascular disease (CVD) events in such patients, are yet to be clarified. METHODS: This ongoing trial is a multicenter, prospective, observational study of non-dialysis CKD patients with renal anemia. The primary objective is to survey the current realities of the therapy with ESA in Japan and evaluate the correlation between hyporesponsiveness to darbepoetin alfa and CKD progression. The secondary objective is to investigate relationship between ESA hyporesponsiveness and CVD events based on the clinical situation in Japan, and to explore an ESA response index. RESULTS: The subjects consist of CKD patients with estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m2 who present renal anemia. The target number of registered cases is 2000 patients, based on estimates of incidences of renal and CVD events from past studies. Renal function and CVD events will be observed for 96 weeks after the initiation of darbepoetin alfa administration. Definitions of ESA hyporesponsiveness will also be investigated. CONCLUSION: By clarifying markers and factors involved in ESA hyporesponsiveness and their relationships with renal and CVD events, this ongoing study aims to improve evidence-based therapies for renal anemia in non-dialysis CKD patients.

Low signal intensity lesions on brain susceptibility-weighted MRI in a patient with intravascular large B-cell lymphoma.

A 71-year-old man was admitted to our hospital because of abnormal behavior and generalized convulsion. Brain MRI revealed no abnormalities upon admission. Levels of serum lactate dehydrogenase and soluble interleukin-2 receptors were significantly elevated, whereas the initial bone marrow puncture and random skin biopsy findings were non-malignant. On the tenth day of admission, brain MRI revealed dot and strip-shaped low signal intensity lesions on susceptibility-weighted images (SWI) disseminated mainly within the cerebral cortex. Administration of high dose methyl-prednisolone improved neither his condition nor these MRI findings. Ground-glass opacities within the bilateral lungs later emerged on the chest CT. The results of a transbronchial lung biopsy and second bone marrow puncture were consistent with a diagnosis of intravascular large B-cell lymphoma (IVLBCL). Despite the lack of histopathological confirmation, the low signal intensities on brain SWI in this case were also considered IVLBCL lesions, reflective of micro-hemorrhagic changes.

[Analysis of Scattered Radiation in an Irradiated Body by Means of the Monte Carlo Simulation: Back-scatter Factors of Diagnostic X-rays in the Incident Surface Which is Not Flat].

To obtain patient entrance surface dose in X-ray photography, a calculation method based on measured exposure or air kerma radiated from X-ray tube is generally used. Two factors are necessary for this calculation: (1) exposure/air kerma to absorb dose conversion factor and (2) back-scatter factor (BSF) based on X-ray quality and on field size. These BSFs are commonly obtained by interpolation from existent data which were given for a water phantom whose entrance surface is flat. Since patient's surface in X-ray photograph is not flat, some error may occur when existent BSF is used in this calculation. In this article, BSF for water phantom with cylindrical surface and elliptic cylinder surface were calculated by means of the Monte Carlo simulation. And these BSFs were compared with BSF for flat surface phantom. As a result (1) radius of curvature of cylindrical phantom or horizontal axis of elliptic cylinder phantom is smaller, (2) half value layer of X-ray is larger, (3) field size is larger, difference of these BSF with that for flat surface phantom tends to be larger. Maximum difference by calculation condition assumed in this article was more than 10%. The cause of this difference is because scattering volume in irradiated body of cylindrical or elliptic cylinder phantom is smaller than flat surface phantom. To obtain patient entrance surface dose more precisely, it is necessary to use BSF respectively calculated for phantom resembling patient's body such as cylindrical or elliptic cylinder phantom by means of the Monte Carlo simulation.

Diagnostic value of procalcitonin for acute complicated appendicitis.

A rapid and reliable test for detection of complicated appendicitis would be useful when deciding whether emergency surgery is required. We investigated the clinical usefulness of procalcitonin for identifying acute complicated appendicitis. We retrospectively analyzed 63 patients aged ≥15 years who underwent appendectomy without receiving antibiotics before admission and had preoperative data on the plasma procalcitonin level (PCT), body temperature (BT), white blood cell count (WBC), neutrophil / lymphocyte ratio (N/L ratio), and C-reactive protein level (CRP). Patients were classified into 3 groups: group A (inflammatory cell infiltration of the appendix with intact mural architecture), group B (inflammatory cell infiltration with destruction of mural architecture, but without abscess or perforation), and group C (macroscopic abscess and/or perforation). For identifying destruction of mural architecture, the diagnostic accuracy of PCT was similar to that of BT or CRP. However, the diagnostic accuracy of PCT was highest among the five inflammatory indices for identifying abscess and/or perforation, with the positive predictive value of PCT for abscess and/or perforation being higher than that of CRP (73% vs. 48%). Univariate analysis of the predictors of abscess and/or perforation revealed that a plasma PCT level ≥0.46 ng/mL had the highest odds ratio (30.3 [95% confidence interval: 6.5-140.5] versus PCT <0.46 ng/mL). These findings indicate that procalcitonin is a useful marker of acute appendicitis with abscess and/or perforation.

[Analysis of Scattered Radiation in an Irradiated Body by Means of the Monte Carlo Simulation: Variation of the Subjective Contrast Due to Difference in the Location of Inhomogeneous Region].

When an inhomogeneous medium such as bone, whose composition or density are clearly different from that of soft tissue of human body, exist in irradiated body, a subjective contrast of X-ray image changes by the location of these inhomogeneous medium. This cause due to the change of behavior of scattered photons in the body depends on the location of inhomogeneous medium besides due to the influence of a penumbra. But this mechanism is not explained clearly yet. In this paper, it was analyzed by means of the Monte Carlo simulation that what kind of difference occurs to a subjective contrast by the difference in location of inhomogeneous medium in water phantom and that a change in behavior of scattered photons in the phantom influences a subjective contrast by what kind of mechanism. In this case the inhomogeneous medium is bone, whose effective atomic number and density are higher than that of water, the subjective contrast of X-ray image degrades when bone is located near the entrance surface (upper position) than located near the exit surface (lower position). This is caused by the number of scattered photons, originated in primary photons incident upon the zone besides the region from entrance surface to exit surface including inhomogeneous medium and incident on the area of shadow of inhomogeneous medium on the image detector, is greater in case of the upper position than in case of the lower position. In the lower position, many of these scattered photons are interacted in bone located near the exit surface by the photo-electric absorption and only a small amount is incident on the image detector.

Rapid Deterioration of the Renal Function Caused by the Coexistence of Intratubular Amyloidosis and Myeloma Cast Nephropathy.

Multiple myeloma presents with various kidney injuries, including cast nephropathy, light chain deposition disease, and amyloidosis. Cast nephropathy is the most common form and mostly consists of monoclonal immunoglobulin light chains with Tamm-Horsfall protein. Immunoglobulin light chain (AL) amyloidosis may affect all compartments of the kidney, but it is rare in the tubuli. We herein present a rare case with rapid progression of renal failure caused by the co-occurrence of intratubular amyloidosis and cast nephropathy due to multiple myeloma. Our case suggests unique amyloidogenic light chain cast, which can form amyloid fibrils under specific tubular fluid conditions, and illustrates the complicated light chain pathophysiology.

[A case of eosinophilic myositis presenting with myocarditis and cardiac embolism].

We report the case of a 72-year-old male who presented with the complaints of muscular pain and weakness. The patient showed marked eosinophilia, elevated levels of myogenic enzymes and pathological abnormalities including eosinophil infiltration obtained from the muscle biopsy. Based on these findings, the patient was diagnosed with eosinophilic myositis. During follow-up, left ventricular wall motion abnormalities with transient electrocardiographic abnormalities were identified; these were believed to be concurrent with eosinophilic myocarditis. Further, notable complications included cardiogenic cerebral embolism. Eosinophilic myositis has been found to cause a wide spectrum of complications. Our findings indicate that in cases of suspected eosinophilic myositis, it is crucial to identify myocarditis immediately and to select an anticoagulant therapy to prevent cerebral embolism.

Photon mass energy transfer coefficients for elements z=1 to 92 and 48 additional substances of dosimetric interest.

Photon mass energy transfer coefficient is an essential factor when converting photon energy fluence into kinetic energy released per unit mass (kerma). Although mass attenuation coefficient and mass energy absorption coefficients can be looked up in databases, the mass energy transfer coefficient values are still controversial. In this paper, the photon mass energy transfer coefficients for elements Z=1-92 were calculated based on cross-sectional data for each photon interaction type. Mass energy transfer coefficients for 48 compounds and/or mixtures of dosimetric interest were calculated from coefficient data for elements using Bragg's additivity rule. We additionally developed software that can search these coefficient data for any element or substance of dosimetric interest. The database and software created in this paper should prove useful for radiation measurements and/or dose calculations.

Therapeutic dose of acetaminophen as a possible risk factor for acute kidney injury: learning from two healthy young adult cases.

Acetaminophen overdose can lead to severe liver and kidney failure; however, the risk of therapeutic doses in healthy individuals causing acute kidney injury (AKI) is less clear. We herein describe the cases of two young adults with renal biopsy-proven acute tubular necrosis under a therapeutic dose of acetaminophen. The first patient exhibited mild reversible renal insufficiency, whereas, in the second case, the patient demonstrated a slightly increased serum creatinine level and enlarged kidneys and the administration of contrast media and antibiotics may have worsened the renal dysfunction, leading to the need for temporal hemodialysis. Physicians should be aware of the risk of acetaminophen causing AKI and avoid administering other nephrotoxic agents in such cases.

A multicenter cross-sectional study of circulating soluble urokinase receptor in Japanese patients with glomerular disease.

Elevated serum-soluble urokinase receptor (suPAR) levels have been described in patients with focal segmental glomerulosclerosis (FSGS) in several different cohorts. However, it remains unclear whether this is the case for Japanese patients and whether circulating suPAR can be clinically useful as a diagnostic marker. To determine this, we measured serum suPAR levels in 69 Japanese patients with biopsy-proven glomerular diseases in a cross-sectional manner. The serum suPAR levels showed a significant inverse correlation with renal function by univariate (R(2) of 0.242) and multivariate (ß=0.226) analyses. Even after excluding patients with renal dysfunction, no significant difference in the suPAR levels was detected among the groups. Receiver operating characteristic analysis and measures of the diagnostic test performance showed that suPAR was not a useful parameter for differentiating FSGS from the other glomerular diseases (AUC-ROC: 0.621), although a small subgroup analysis showed that patients with FSGS, treated with steroids and/or immunosuppressants, had significantly lower suPAR levels. Patients with ANCA-associated glomerulonephritis had significantly higher levels of suPAR compared with the other disease groups, which may be owing to their lower renal function and systemic inflammation. Thus, suPAR levels are significantly affected by renal function and have little diagnostic value even in patients with normal renal function.

[Presumption of the energy-spectrum of high-energy electron beam based on the beta-distribution model].

The energy spectra of high-energy electron beams used in radiotherapy are the most important data for evaluating absorbed doses and/or dose distributions in the body of a patient. However, it is impossible to measure the actual spectra of a high-energy electron beam. In this study, we suggest a method to presume the spectra of high-energy electron beams by use of the beta distribution model. The procedure of this method is as follows: (1) the spectrum of the high-energy electron beam was assumed to have a maximum energy Emax, and α, ß parameters of the beta probability density function. (2) The percentage depth dose (PDD) based on the assumed spectrum was calculated by a Monte Carlo simulation. (3) The best matching energy spectrum was searched in comparison with the experimental PDD curves. Finally, the optimal energy spectrum of the electron beam was estimated after reiterating the process from (1) to (3). With our method, the measured PDD curves were optimally simulated following the experimental data. It appeared that the assumed spectra approximated well to the actual spectra. However, the error between the assumed and experimental data was observed in the region under the incident surface. We believe this was due to the influence of low-energy electrons scattered at installed collimators, etc. In order to simulate PDDs in this region accurately, a further correction process is required for a spectrum based on the beta distribution model.

[Detailed analysis of multi-leaf collimator movement during radiation delivery using an in-house-developed program].

Multi-leaf collimators (MLCs) are used to modulate intensity during intensity modulated radiation therapy (IMRT). Evaluation of MLC movement in IMRT is important, since the accuracy of MLC movements affects the dose distribution. This evaluation is conventionally performed using an attached Dynalog File Viewer (DFV). However, due to its being an overall evaluation, it is not possible to discover significant errors. In this study, we developed software that permits easy analysis of MLC movements that can be used to retrospectively evaluate MLC movement during irradiation. We also evaluated the usefulness of our in-house program and confirmed its potential for use in clinical scenarios. We created a program that can read MLC logfiles using Visual Basic 6.0 and visualize the temporal changes and movements of the MLC. To evaluate our in-house program's efficacy in analyzing dynamic MLC-QA (quality assurance), we compared the numerical results yielded by our in-house program and the DFV. The results showed that our in-house program was able to reveal errors below the error root mean square (RMS) values obtained using the DFV. Using irregular surface compensator (ISC) irradiation conditions in a clinical context, we compared our in-house program with the DFV and, using RMS analysis, identified cases that showed excessive error. Our in-house program can also be used to investigate whether unacceptable errors are present, as well as their cause, when using the MLC, as it allows easy real-time observation and evaluation of MLC movements. An additional benefit is that collecting the MLC logfile during actual treatment also allows it to be evaluated retrospectively after continuous MLC operation.