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Background: The East Asian-specific genetic diversity, the rs671 variant of aldehyde dehydrogenase 2, causes the “Asian flush” phenomenon following alcohol consumption, resulting in an alcohol avoidance phenotype. The variant is suggested as a risk factor for Alzheimer’s disease; however, its association with mild cognitive impairment (MCI), an effective target for secondary prevention of dementia, remains unclear. Method: This cross-sectional study examined 430 individuals aged 60–80 years (251 women) without overt cognitive impairment in Yoshinogari, Japan. The effect of the rs671 variant on MCI, defined by scores

Abstract Background The aim of the present study was to use surgical and histological results to develop a simple noninvasive technique to improve nodal staging using preoperative PET/CT in patients with resectable lung cancer. Methods Preoperative PET/CT findings (pStage IB–III 182 patients) and pathological diagnoses after surgical resection were evaluated. Using PET/CT images to determine the standardized uptake value (SUV) ratio, the SUVmax of a contralateral hilar lymph node (on the side of the chest opposite to the primary tumor) was measured simultaneously. The I/C‐SUV ratio was calculated as ipsilateral hilar node SUV/contralateral hilar node SUV. Receiver operating characteristic (ROC) curves were then used to analyze those data. Results Based on ROC analyses, the cutoff I/C‐SUV ratio for diagnosis of lymph node metastasis was 1.34. With a tumor ipsilateral lymph node SUVmax ≥2.5, an IC‐SUV ratio ≥1.34 had the highest accuracy for predicting N1/N2 metastasis; the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of nodal staging were 60.66, 85.11, 84.09, 62.5 and 71.29%, respectively. Conclusions When diagnosing nodal stage, a lymph node I/C‐SUV ratio ≥1.34 can be an effective criterion for determining surgical indications in advanced lung cancer.

Surgical management has a direct impact on the quality treatment of patients and the economic efficiency of hospitals. Surgeries are managed in hospitals according to the duration of surgery reported by the surgeons. Surgical management efficiency would improve if the duration could be predicted accurately. This study focuses on predicting the individual duration in surgical management. The data on 9567 surgical cases from the National Cancer Center Hospital Japan East illustrates hospital characteristics and forecasts the duration requirements using a machine learning algorithm. We obtain an adjusted coefficient of determination exceeding 0.7 and show the relationship between the hospital characteristics and duration in a case-mix classification framework. We also discuss the relationship between data characteristics and the prediction accuracy of machine learning. This study supports operating room managers when they predict surgical duration by machine learning in ascertaining data characteristics, understanding the prediction accuracy of machine learning, and predicting surgical duration more accurately.

We evaluated treatment outcomes of external beam radiation therapy (EBRT) for unresectable locally advanced thyroid cancer (LATC) with or without metastasis. We enrolled 11 LATC patients who underwent EBRT (median age: 76 (45–83) years; six males and five females). Eastern Cooperative Oncology Group performance statuses of 0 (n = 3), 1 (n = 1), 2 (n = 6), and 3 (n = 1) were observed. Histologic types included papillary carcinoma (n = 5), anaplastic carcinoma (n = 3), and squamous cell carcinoma (n = 3). The organs invaded by the tumor that caused it to be deemed unresectable were common carotid artery (n = 5), trachea (n = 4), aorta (n = 1) and larynx (n = 1). The median follow-up time was 6 months. One, seven, two, and one patient showed complete response (CR), partial response (PR), stable disease, and progressive disease, respectively. The rate of local CR+PR was 73%; moreover, 75% of patients achieved a >30% tumor size reduction within 6 months. The median local progression-free survival of patients with local CR+PR was 11.5 (4–68) months. The median overall survival was 6 (1–68) months. Grade 3 acute complications occurred in five (45%) patients. No patients had Grade 4 or 5 complications. In conclusion, EBRT reduced the tumor volume in 75% of LATC patients without inducing severe toxicity. This therapy should be considered as a treatment option for LATC.

Abstract I have been conducting a study of postseismic deformation following the 2016 Kumamoto earthquake using ALOS-2/PALSAR-2 acquired till 2018. I apply ionospheric correction to interferograms of ALOS-2/PALSAR-2. L-band SAR gives us high coherence enough to reveal surface deformation even in vegetated or mountainous area for pairs of images acquired more than 2 years. Postseismic deformation following the Kumamoto earthquake exceeds 10 cm during 2 years at some spots in and around Kumamoto city and Aso caldera. Westward motion of ~ 6 cm/year was dominant on the southeast side of the Hinagu fault, while westward shift was detected on both sides of the Futagawa fault. The area of latter deformation seems to have correlation with distribution of pyroclastic flow deposits. Significant uplift was found around the eastern Futagawa fault and on the southwestern frank of Aso caldera, whose rate reaches 4 cm/year. There are sharp changes across several coseismic surface ruptures such as Futagawa, Hinagu, and Idenokuchi faults. Rapid subsidence between Futagawa and Idenokuchi faults also found. It is confirmed that local subsidence continued along the Suizenji fault, which newly appeared during the mainshock in Kumamoto City. Subsidence with westward shift of up to 4 cm/year was also found in Aso caldera. Time constant of postseismic decay ranges from 1 month to 600 days at selected points, but that postseismic deformation during the first epochs or two is dominant at point in the Kumamoto Plain. This result suggests multiple source of deformation. Westward motion around the Hinagu fault may be explained with right lateral afterslip on the shallow part of this fault. Subsidence along the Suizenji fault can be attributed to normal faulting on dipping westward. Deformation around the Hinagu and Idenokuchi faults cannot be explained with right lateral afterslip of Futagawa fault, which requires other sources. Deformation in northern part of Aso caldera might be the result of right lateral afterslip on a possible buried fault.

We present the case of a 22-year-old man who was diagnosed with tonsillitis and treated with antibiotics. Although the symptoms subsided, 1 week later, he presented with weakness in the lower limbs and was hospitalized. The weakness in the lower limbs worsened; he developed difficulty speaking and was transferred to our hospital. Laboratory tests showed a white blood cell count of 10,600/μL (24% atypical lymphocytes). Positive results were obtained for immunoglobulin M (IgM) antibody against Epstein-Barr virus (EBV) viral capsid antigen. EBV-deoxyribonucleic acid quantification in blood yielded positive results. Magnetic resonance imaging (MRI) revealed a hyperintensity in the spinal cord at the Th11 level of the lower spine on T2-weighted imaging (T2WI). In addition, T2WI and fluid-attenuated inversion recovery imaging showed hyperintense lesions on the right cerebral peduncle, bilateral thalami, posterior leg of the left internal capsule, and right corona radiata. We diagnosed acute disseminated encephalomyelitis (ADEM) with EBV and initiated steroid pulse therapy. Symptoms, along with the lesions seen on MRI, subsequently ameliorated. This case suggests that ADEM can be difficult to diagnose, but careful diagnosis is crucial since appropriate treatment is necessary to improve the symptoms.

Abstract Active faults commonly repeat cycles of sudden rupture and subsequent silence of hundreds to tens of thousands of years, but some parts of mature faults exhibit continuous creep accompanied by many small earthquakes. Discovery and detailed examination of creeping faults on land have been in a rapid progress with the advent of space-borne synthetic aperture radar interferometry. In this study, we measured the spatial variation of the creep rate along the Philippine fault on Leyte Island using ALOS/PALSAR data acquired between October 2006 and January 2011. Prominent creep of $$33\pm {11}$$ 33±11 mm/year was estimated in northern and central parts of the island except for a locked portion around latitude 11.08–11.20$$^\circ$$ ∘ N. We compared the creep rate distribution along the fault with the slip distribution of the 2017 $$M_w$$ Mw 6.5 Ormoc earthquake which occurred in northern Leyte, estimated from the displacements mapped by ALOS-2/PALSAR-2 interferometric data. The estimated slip of the 2017 earthquake amounted up to 2.5 m and to moment magnitude of 6.49, with the dominant rupture area coinciding with the locked portion identified from the interseismic coupling analysis. Teleseismic waveforms of the 2017 earthquake and another event that occurred in 1947 ($$M_s$$ Ms 6.9) exhibit close resemblance, indicating two ruptures of rather similar locations and magnitudes with a time interval of 70 years.

Abstract Background Determining the appropriate gross tumor volume is important for irradiation planning in addition to palliative radiation for bone metastases. While irradiation planning is commonly performed using simulation computed tomography (CT), magnetic resonance imaging (MRI), bone scintigraphy, and 18fluorodeoxyglucose-positron emission tomography-CT (18FDG-PET-CT) are more sensitive for detecting bone metastasis and invasion areas. Therefore, this study evaluated whether pretreatment imaging modalities influenced the response to palliative radiation therapy (i.e., the irradiation effect) for painful bone metastases from solid malignant carcinomas. Methods Consecutive patients with painful bone metastases treated with palliative radiation between January 2013 and December 2017 at our institution were included. We retrospectively investigated the pretreatment images from the different imaging modalities (CT, MRI, bone scintigraphy, and 18FDG-PET-CT) obtained between 1 month before and the initiation of palliative radiation and determined the primary site of carcinoma, histological type, metastatic lesion type (osteolytic, osteoblastic, or mixed), pathological fracture, and metastatic site (vertebral or not). We then evaluated the relationship between these factors and treatment response. We defined “response” as the condition in which patients achieved pain relief or reduced the use of painkiller medicines. Results In total, 131 patients (78 men and 53 women) were included; the median age was 66 years (range, 24–89 years). Prescribed doses were 8–50 Gy/1–25 fractions with 2–8 Gy/fraction. Among the 131 patients, 105 were responders (response rate, 80%). The imaging modalities performed before irradiation were CT in 131 patients, MRI in 54, bone scintigraphy in 56, and 18FDG-PET-CT in 14. The Welch t-test and chi-square test showed no significant association between treatment response and each factor. Multiple logistic regression analysis including the imaging modality, metastatic site, and pathological fracture also showed no significant association with each factor. Conclusions There was no significant relationship between the type of pretreatment imaging and treatment response for painful bone metastases. Thus, setting the appropriate radiation field according to CT images and clinical findings could help avoiding further image inspection before palliative radiation for painful bone metastases.

Abstract The release of ATP from the epithelium of the urinary bladder (urothelium) in response to mechanical/chemical stimuli contributes to the visceral sensation in the micturition reflex. The nitric oxide (NO)‐mediated induction of cyclic guanosine monophosphate (cGMP) has been detected in urothelial cells and may inhibit the micturition reflex. However, the function of the NO‐cGMP pathway in the regulation of urothelial ATP release remains poorly understood in contrast to its effects on smooth muscles or primary afferent nerves. Therefore, we investigated the relevance of the NO‐cGMP pathway to ATP release on the mucosal side in the present study. The administration of l‐arginine (NO precursor) or NOC 12 (NO donor) significantly reduced ATP release to the mucosal side at a physiologically normal urine storage pressure (5 cmH2O). L‐NAME (NO synthase inhibitor) significantly increased the distention‐induced release of ATP. The phosphodiesterase‐5 inhibitor, sildenafil, which increases cGMP levels, inhibited distention‐induced ATP release. Furthermore, sildenafil significantly reduced ATP release in response to the administration of lipopolysaccharide. These results suggest that the NO‐cGMP pathway inhibited urothelial ATP release during the storage phase under both physiological and pathological conditions.

Abstract Coseismic surface deformation imaged through interferometric synthetic aperture radar (InSAR) measurements was used to estimate the fault geometry and slip distribution of the 2017 Mw 6.5 Ormoc earthquake along a creeping segment of the Philippine Fault on Leyte Island. Our best fitting faulting model suggests that the coseismic rupture occurred on a fault plane with high dip angle of 78.5° and strike angle of 325.8°, and the estimated maximum fault slip of 2.3 m is located at 6.5 km east‐northeast of the town of Kananga. The recognized insignificant slip in the Tongonan geothermal field zone implies that the plastic behavior caused by high geothermal gradient underneath the Tongonan geothermal field could prevent the coseismic failure in heated rock mass in this zone. The predicted Coulomb failure stress change shows that a significant positive Coulomb failure stress change occurred along the SE segment of central Philippine Fault with insignificant coseismic slip and infrequent aftershocks, which suggests an increasing risk for future seismic hazard.

Autophagy is an evolutionarily conserved mechanism for the gross disposal of intracellular proteins in mammalian cells and dysfunction in this pathway has been associated with human disease. Although the serine threonine kinase Akt is suggested to play a role in this process, little is known about the molecular mechanisms by which Akt induces autophagy. Using a yeast two-hybrid screen, Phafin2 (EAPF or PLEKHF2), a lysosomal protein with a unique structure of N-terminal PH (pleckstrin homology) domain and C-terminal FYVE (Fab 1, YOTB, Vac 1, and EEA1) domain was found to interact with Akt. A sucrose gradient fractionation experiment revealed that both Akt and Phafin2 co-existed in the same lysosome enriched fraction after autophagy induction. Confocal microscopic analysis and BiFC analysis demonstrated that both Akt and Phafin2 accumulate in the lysosome after induction of autophagy. BiFC analysis using PtdIns (3)P interaction defective mutant of Phafin2 demonstrated that lysosomal accumulation of the Akt-Phafin2 complex and subsequent induction of autophagy were lysosomal PtdIns (3)P dependent events. Furthermore, in murine macrophages, both Akt and Phafin2 were required for digestion of fluorescent bacteria and/or LPS-induced autophagy. Taken together, these findings establish that lysosomal accumulation of Akt and Phafin2 is a critical step in the induction of autophagy via an interaction with PtdIns (3)P.

Bacillus cereus (B. cereus) is a pathogen in opportunistic infections. Here we show that Bacillus cereus sphingomyelinase (Bc-SMase) is a virulence factor for septicemia. Clinical isolates produced large amounts of Bc-SMase, grew in vivo, and caused death among mice, but ATCC strains isolated from soil did not. A transformant of the ATCC strain carrying a recombinant plasmid containing the Bc-SMase gene grew in vivo, but that with the gene for E53A, which has little enzymatic activity, did not. Administration of an anti-Bc-SMase antibody and immunization against Bc-SMase prevented death caused by the clinical isolates, showing that Bc-SMase plays an important role in the diseases caused by B. cereus. Treatment of mouse macrophages with Bc-SMase resulted in a reduction in the generation of H(2)O(2) and phagocytosis of macrophages induced by peptidoglycan (PGN), but no effect on the release of TNF-α and little release of LDH under our experimental conditions. Confocal laser microscopy showed that the treatment of mouse macrophages with Bc-SMase resulted in the formation of ceramide-rich domains. A photobleaching analysis suggested that the cells treated with Bc-SMase exhibited a reduction in membrane fluidity. The results suggest that Bc-SMase is essential for the hydrolysis of SM in membranes, leading to a reduction in phagocytosis.

Imatinib mesylate is a tyrosine kinase inhibitor of c-KIT and PDGFRA. Imatinib mesylate is an effective drug that can be used as a first-choice agent for treatment of GISTs. Prior to treatment, molecular diagnosis of c-KIT or PDGFRA is necessary; however, in some types of GISTs, it is impossible to obtain a sufficient amount of specimen for diagnosis. An inoperable or marginally resectable GIST in a 79-year-old female was difficult to be diagnosed at a molecular pathological level, and hence, exploratory treatment was initiated using imatinib combined with 18FDG-PET evaluation at 1-month intervals. PET imaging indicated a positive response, and so we continued imatinib treatment in an NAC setting for 4 months. As a result, curative resection of the entire tumor was successfully performed with organ preservation and minimally invasive surgery. 18FDG-PET evaluation at 1-month intervals is beneficial for GISTs that are difficult to be diagnosed histopathologically.