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Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a clinically aggressive hematologic malignancy derived from plasmacytoid dendritic cells. It commonly presents as cutaneous lesions. To date, no standard treatment protocol for BPDCN exists. Traditionally treated similarly to acute leukemia or lymphoma, its prognosis remains poor. Radiation therapy is employed for isolated skin lesions, for patients that are ineligible for chemotherapy due to age or comorbidities and for post-chemotherapy recurrence. However, very limited reports are available on radiotherapy for BPDCN. We present a case involving a 94-year-old BPDCN patient treated with radiation therapy, highlighting an atypical situation of two separate radiotherapy sessions with different dosages for isolated skin lesions. Initially, 45 Gy was administered in 15 fractions (45 Gy/15 Fr), followed by a second session of 30 Gy in 10 fractions (30 Gy/10 Fr) after disease recurrence. This case is unique in detailing radiation therapy for the exceedingly rare BPDCN, particularly dose fractionation. The findings indicate that 45 Gy/15 Fr can provide adequate local control, while even a lower dose of 30 Gy/10 Fr may be effective. This case report contributes to the limited literature by proposing potential therapeutic approaches and dosage guidelines to refine future BPDCN treatment protocols.

Abstract Background Intrahepatic cholangiocarcinoma (ICC) is a challenging primary liver cancer with a poor prognosis, especially in unresectable cases. Traditional palliative irradiation is limited in reducing liver doses. This study aimed to evaluate the efficacy and toxicity of respiratory-gated proton beam therapy without fiducial markers for intrahepatic cholangiocarcinoma. Methods Between October 2011 and February 2022, 24 patients (median [range] age, 71 [41–88] years) were evaluated at our institution. Twelve patients were pathologically diagnosed with ICC. All patients underwent respiratory-gated proton beam therapy at a dose of 48–83.6 (relative biological effectiveness) in 20–38 fractions with four-dimensional computed tomography planning. The median follow-up period was 18.5 (range, 2.0–74.0) months. The median tumor size was 41 (range, 10–134) mm. Twenty-one patients were classified as having Child–Pugh class A, and three patients were classified as having Child–Pugh class B. Local progression was defined as any growth of the irradiated tumor. Results The median survival time was 28 months for all patients. The Kaplan–Meier estimates of the 2-year overall survival, progression-free survival, and local tumor control rates were 51%, 26%, and 73%, respectively. Local tumor control rates were non-inferior to those reported in previous studies using fiducial markers. One patient had grade 4 pleural effusion; however, whether this was an adverse event due to the proton beam therapy was unclear. Conclusions Respiratory-gated proton beam therapy without fiducial markers is an effective and less invasive treatment option for ICC, showing potential for improved local control and tolerable adverse effects.

Abstract Background The 3-variable number-of-risk-factors (NRF) model is a prognostic tool for patients undergoing palliative radiotherapy (PRT). However, there is little research on the NRF model for patients with painful non-bone-metastasis tumours treated with PRT, and the efficacy of the NRF model in predicting survival is unclear to date. Therefore, we aimed to assess the prognostic accuracy of a 3-variable NRF model in patients undergoing PRT for bone and non- bone-metastasis tumours. Methods This was a secondary analysis of studies on PRT for bone-metastasis (BM) and PRT for miscellaneous painful tumours (MPTs), including non-BM tumours. Patients were grouped in the NRF model and survival was compared between groups. Discrimination was evaluated using a time-independent C-index and a time-dependent area under the receiver operating characteristic curve (AUROC). A calibration curve was used to assess the agreement between predicted and observed survival. Results We analysed 485 patients in the BM group and 302 patients in the MPT group. The median survival times in the BM group for groups I, II, and III were 35.1, 10.1, and 3.3 months, respectively (P

A 53-year-old female with primary biliary cholangitis was referred for the evaluation of a hepatic nodule identified during routine imaging. Ultrasonography revealed a homogeneous, hypoechoic, 18 mm nodule in segment 3 of the liver. On dynamic CT and MRI, the nodule showed mild enhancement at the hepatic artery-dominant phase. On diffusion-weighted images, the nodule exhibited pronounced hyperintensity with accompanying wedge-shaped perinodular hyperintensity (comet and comet-tail appearance). The nodule showed a portal perfusion defect on CT during arterial portography, and mild enhancement on CT during hepatic arteriography (CTHA). A nodular and wedge-shaped perinodular enhancement (comet and comet-tail appearance) in the CTHA was also clearly observed. The nodule demonstrated abnormal FDG uptake on 18F-FDG-PET/CT. An excisional biopsy was performed for histopathological diagnosis, and the nodule was diagnosed as reactive lymphoid hyperplasia (RLH). Diagnosing hepatic RLH by imaging is challenging due to its imaging findings overlapping with those of various malignant tumors, especially the nodular type of lymphomas, making differentiation particularly difficult. However, radiologists should note the perinodular early enhancement and the perinodular hyperintensity on diffusion weighted images, which are thought to be key imaging findings of RLH, along with other characteristics such as a single, small, homogeneous nodule with mild early enhancement and marked restricted diffusion. We propose to name the nodular lesion with perinodular early enhancement/hyperintensity on diffusion weighted images as 'comet and comet-tail appearances'.

BackgroundQuality-of-life (QOL) is important for cancer patients with poor prognosis. However, conducting a QOL survey with patients is difficult. Therefore, we conducted a QOL survey with physicians. Specifically, this study aimed to clarify how physicians assess QOL in patients with pancreatic cancer by conducting a survey and comparing the results between physicians and the general public.MethodsA survey was conducted by interviewing physicians administering chemotherapy to patients for recurrent/metastatic pancreatic cancer. This method is similar to that of the QOL survey conducted among the general public. Responses were evaluated using the composite time trade-off (cTTO) and the visual analog scale (VAS) for 11 pancreatic cancer status scenarios (survey scenarios). These scenarios consisted of patients’ health states as well as the types and grades of adverse events (AEs). Health status was classified into two categories: Stable disease (SD) and Progressive disease (PD). In addition, we conducted a survey using the EuroQol 5 Dimensions 5-Level (EQ-5D-5l) as reference values.ResultsTwenty physicians responded to the survey. SD had the highest mean QOL value for both assessment methods (Physicians: 0.78, General public: 0.63), whereas PD had the lowest mean QOL value (Physicians: 0.15, General public: −0.12). The physicians assigned higher QOL values on both the VAS and cTTO than the general public did in all survey scenarios.ConclusionsThe QOL values obtained from physicians were consistent with the degree of status in any assessment scenarios. Based on the differences in the QOL survey results between physicians and the general public, physicians tended to assign higher QOL values than the general public in cTTO and VAS assessments.

Abstract Objectives Schwannoma expansion after radiotherapy has not been well-studied despite the clinical importance of distinguishing transient increase from permanent expansion. Thus, this study aimed to identify the underlying mechanism and novel radiological predictors of schwannoma expansion after radiotherapy. Materials & methods We retrospectively examined the therapeutic effects of radiotherapy on schwannomas and magnetic resonance images of 43 patients with vestibular schwannomas who underwent stereotactic radiotherapy or radiosurgery at our facility between June 1, 2012 and September 1, 2018. Based on the size change pattern, the treated tumors were classified into six groups, including transient-expansion and consistent-increase groups. The apparent diffusion coefficient (ADC) ratio and appearance of any notch were included as evaluation items based on our hypothesis that transient expansion is due to edema with increased extracellular free water. A log-rank test was performed to evaluate the relationship between the local control rate and radiological signs. Results The mean overall 5-year local control rate was 90%, and the median follow-up period was 62 (24–87) months. Approximately 28% of the tumors showed transient expansion; all ADC ratios synchronized with size change, and 75% showed a new notch appearance. Approximately 9% of tumors showed consistent increase, with no notch on the outline. The log-rank test revealed a difference in the local control rate with or without notch appearance in expanding irradiated schwannomas. All tumors with notch appearance showed a significant regression 5 years after radiation. Conclusions New notch appearance on the outline could indicate favorable long-term outcomes of expanding schwannomas post-treatment. Clinical relevance statement Notch appearance can help differentiate a transient schwannoma from a real tumor expansion, and it is a novel predictor of better outcomes of expanding schwannomas after radiotherapy. Graphical Abstract

Purpose: This study examines periductal infiltration in intrahepatic mass-forming cholangiocarcinoma (IMCC), focusing on its importance for differentiating hepatic tumors and its influence on post-surgical survival in IMCC patients. Methods: Eighty-three consecutive patients with IMCC (n = 43) and liver cancer whose preoperative images showed intrahepatic bile duct dilatation adjacent to the tumor for differential diagnosis from hepatocellular carcinoma (HCC) [n = 21], metastatic liver cancer (MLC) [n = 16] and combined hepatocellular-cholangiocarcinoma (cHCC-CC) [n = 3] were enrolled. CT and MRI findings of simple bile duct compression, imaged periductal infiltration, and imaged intrabiliary growth adjacent to the main tumor were reviewed. Clinicopathological and imaging features were compared in each group. The sensitivity, specificity, and odds ratio were calculated for each imaging finding of IMCC versus the other tumor groups. Overall survival was compared between cases of IMCC with and without imaged periductal infiltration. Results: Simple bile duct compression and imaged intrabiliary growth were more frequently observed in HCC than in the others (p

Abstract This study assessed the clinical performance of point-of-care testing (POCT) for quick cortisol assay (QCA) during adrenal vein sampling (AVS) using a newly invented portable quantitative assay instrument. An observational study was conducted prospectively at two centres in Japan. Forty-eight patients with primary aldosteronism considered for adrenalectomy were enrolled in this study and underwent AVS. Three basal adrenal vein samples from each adrenal vein and two from the inferior vena cava were collected sequentially. The cortisol concentration of adrenal vein samples was measured by routine method and QCA. A total of 338 adrenal vein samples were analysed from 250 sites to determine AVS success or failure. The distribution of turnaround time of the QCA for AVS success or failure followed a normal distribution with an average of 20.5 min. A positive correlation between the routine method and QCA was observed regarding cortisol concentration or selectivity index. No significant difference between the two methods was observed regarding the success rate of AVS. Using the routine method as a reference, the sensitivity and specificity of AVS success or failure were 99.1% (210/212) and 81.6% (31/38), respectively. Easy, quick, portable, and precise POCT-QCA demonstrated its compatibility with routine methods regarding clinical performance.

Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers, and surgical resection is the only potentially curative approach. However, the rate of recurrence remains high, particularly within the first 6 months, and is associated with a poor prognosis. The present study evaluated the clinical characteristics and risk factors for early recurrence in pancreatic ductal adenocarcinoma (PDAC) patients who underwent curative resection, regardless of the use of neoadjuvant chemotherapy, to identify predictive factors associated with early recurrence and poor outcomes as well as to determine the optimal treatment strategy for patients at high risk of early recurrence after surgical resection. Methods Patients who underwent pancreatic resection for PDAC at our institution from 2013 to 2021 were included in this study. We investigated the clinicopathological features of patients in groups: those with recurrence within 6 months, recurrence between 6 and 12 months, and recurrence beyond 12 months or no recurrence. A logistic regression analysis identified covariates associated with early recurrence at 6 and 12 months. Results The study included 403 patients with a median follow-up of 25.7 months. Recurrence was observed in 279 patients, with 14.6% recurring within 6 months, 23.3% within 6–12 months, and 62% after 12 months or not at all. The preoperative CA19-9 level, modified Glasgow prognostic score (mGPS), and positive peritoneal cytology were significant risk factors for early recurrence within 6 months, while positive peritoneal cytology, lymph node metastasis, and the absence of adjuvant chemotherapy were significant risk factors for recurrence within 12 months. For patients who received preoperative chemotherapy or chemoradiotherapy, the preoperative CA19-9 level, mGPS, and positive peritoneal cytology were significant independent risk factors for early recurrence within 6 months, while positive peritoneal cytology, lymph node metastasis, and the absence of adjuvant chemotherapy were significant independent risk factors for recurrence within 12 months. The study concluded that the overall survival after surgical resection for potentially resectable PDAC worsened according to the number of risk factors present in the patient. Conclusions We clarified that preoperative CA19-9, positive peritoneal cytology, and the lack of adjuvant chemotherapy were consistent predictors for early recurrence within 6 and 12 months. In addition, an increased number of risk factors affecting the patient was associated with a poorer overall survival after potentially curable resection. Calculating the number of risk factors for early recurrence may be an essential predictive factor when considering treatment strategies.

Purpose: To assess the feasibility of the 6-point Dixon method for evaluating liver masses. We also report our initial experience with the quantitative values in various liver masses on a 3T system. Materials and methods: Of 251 consecutive patients for whom 6-point Dixon was employed in abdominal magnetic resonance imaging scans between October 2020 and October 2021, 117 nodules in 117 patients with a mass diameter of more than 1 cm were included in the study. Images for measuring the proton density fat fraction (PDFF) and R2 * values were obtained using the iterative decomposition of water and fat with echo asymmetry and least-squares estimation-quantitative technique for liver imaging. Two radiologists independently measured PDFF (%) and R2 * (Hz). Inter-reader agreement and the differences between readers were examined using intra-class correlation coefficient (ICC) and the Bland-Altman method, respectively. PDFF and R2 * values in differentiating liver masses were examined. Results: The masses included hepatocellular carcinoma (n = 59), cyst (n = 20), metastasis (n = 14), hemangioma (n = 8), and others (n = 16). The ICCs for the region of interest (mm2), PDFF, and R2 * were 0.988 (95 % confidence interval (CI): 0.983, 0.992), 0.964 (95 % CI: 0.949, 0.975), and 0.962 (95 % CI: 0.941, 0.975), respectively. The differences of measurements between the readers showed that 5.1 % (6/117) and 6.0% (7/117) for PDFF and R2 * , respectively, were outside the 95 % CI. Conclusion: Our observation indicates that the 6-point Dixon method is applicable to liver masses.

Abstract Background Fluorouracil, leucovorin (5FU/LV), and nanoliposomal-irinotecan (nal-IRI) combination therapy has been established as the second-line treatment for advanced pancreatic ductal adenocarcinoma. Oxaliplatin with 5FU/LV (FOLFOX) is often used as a subsequent treatment, although its efficacy and safety are yet to be fully elucidated. We aimed to evaluate the efficacy and safety of FOLFOX as a third- or later-line treatment for patients with advanced pancreatic ductal adenocarcinoma. Methods We conducted a single-centre, retrospective study that enrolled 43 patients who received FOLFOX after failure of gemcitabine-based regimen followed by 5FU/LV + nal-IRI therapy between October 2020 and January 2022. FOLFOX therapy consisted of oxaliplatin (85 mg/m2), levo-leucovorin calcium (200 mg/m2) and 5-FU (2400 mg/m2) every 2 weeks per cycle. Overall survival, progression-free survival, objective response, and adverse events were evaluated. Results At the median follow-up time of 3.9 months in all patients, the median overall survival and progression-free survival were 3.9 months (95% confidence interval [CI], 3.1–4.8) and 1.3 months (95% CI, 1.0–1.5), respectively. Response and disease control rates were 0 and 25.6%, respectively. The most common adverse event was anaemia in all grades followed by anorexia; the incidence of anorexia and grades 3 and 4 was 21 and 4.7%, respectively. Notably, grades 3–4 peripheral sensory neuropathy was not observed. Multivariable analysis revealed that a C-reactive protein (CRP) level of > 1.0 mg/dL was a poor prognostic factor for both progression-free survival and overall survival: hazard ratios were 2.037 (95% CI, 1.010–4.107; p = 0.047) and 2.471 (95% CI, 1.063–5.745; p = 0.036), respectively. Conclusion FOLFOX as a subsequent treatment after failure of second-line treatment with 5FU/LV + nal-IRI is tolerable, although its efficacy is limited, particularly in patients with high CRP levels.

Abstract Aims/Introduction Among colorectal cancer (CRC) patients, pre‐existing diabetes is suggested to influence poor prognosis, but the impact on adjuvant chemotherapy implementation is largely unknown. We aimed to compare the implementation rate of adjuvant chemotherapy between CRC patients with and without pre‐existing diabetes in a retrospective cohort study. Materials and Methods Colorectal cancer diagnosis information was obtained from the hospital‐based cancer registry of patients with stage III CRC who underwent curative surgery in 2013 in Japan (n = 6,344). Health claims data were used to identify diabetes and chemotherapy. We examined the association between diabetes and the implementation rate of adjuvant chemotherapy using a generalized linear model adjusted for age, sex, updated Charlson Comorbidity Index, hospital type and prefecture. Furthermore, we applied a mediation analysis to examine the extent to which postoperative complications mediated the association. Results Of the 6,344 patients, 1,266 (20.0%) had diabetes. The mean ages were 68.2 and 71.3 years for patients without and with diabetes, respectively. Compared with those without diabetes, patients with diabetes were less likely to receive adjuvant chemotherapy (crude rate 58.9 and 49.8%; adjusted percentage point difference 4.6; 95% confidence interval 1.7–7.5). The difference was evident for patients aged

Binder jet is one of the metal additive manufacturing methods. In this method, metal powder is used as a raw material, and a metal part is obtained by sintering a green body produced by jetting a binder on a metal powder bed leveled with a roller. Powders produced by the gas atomization method with an average particle size of around 10 μm is mainly used in the binder jetting method for metal additive manufacturing. The water atomization method used in this study has a higher production yield, so the cost of powder is lower than that of gas atomized powder. It is also possible to produce ultra-fine powders. However, there are few studies on the use of water-atomized powder in the binder jetting method. This paper aims to evaluate the basic characterization using water atomized powder for practical use in the binder jetting method. Three different water atomized powders with average particle sizes ranging from 4 μm to 10 μm and the gas atomized powder with an average particle size of 10 μm for comparison were used in the evaluation. The results confirmed that the flowability of water atomized powder decreased as the average particle size became smaller, and the flowability was lower than that of gas atomized powder due to differences in powder shape even at the same average particle size. The apparent density of the green body was found that tapped density of powder had a significant effect. The sintering process confirmed that the green body with smaller average particle size powder had higher sintering performance. This result is in line with the existing theory in the sintering technology using metal powders. It is clear that tap density and powder flowability are important for the practical use of water atomized powder in the binder jetting method.

In this study, we aim to investigate the effect of galvanic corrosion on the mechanical properties of aluminum-CFRP adhesive joints. Aluminum-CFRP, aluminum-aluminum, and CFRP-CFRP adhesive joint specimens were prepared. Subsequently, the specimens were subjected to accelerated aging treatment in a salt spray environment, and the tensile shear adhesive strength, the transition of the failure surface and the deposition state and the components of corrosion products with aging time were quantitatively evaluated. As a result, in aluminum-CFRP adhesive joints under the salt spray, galvanic corrosion of the aluminum substrate occurred within 24 hours, and the adhesive-adherend interfacial strength decreased significantly compared to aluminum-aluminum and CFRP-CFRP adhesive joints. In addition, the failure mode of aluminum-CFRP adhesive joints changed from the mixed failure of interfacial failure, cohesive failure, and fiber tear failure to interfacial failure. Furthermore, it was found that the deposition amount of Al2O3 increased under the influence of the salt spray environment.

In this study, we will report the efficiency of hybrid filler for the mechanical properties and the thermal conductivity of Polyamide-6 (PA6) composite. One of the ways to improve the thermal conductivity of the composite is to add fillers to the matrix, but the excessive filler causes the composite to form aggregation and void. They make the mechanical properties and thermal conductivity decline. As the solution to this problem, to use of hybrid filler is expected to realize the lower filler content of composite with keeping the properties. However, the most efficient ratio of hybrid filler is unclear. In this study, PA6 and filler were composited using a twin-shaft melt-mixing machine. A manual injection molding machine was then used to produce test specimens for thermal conductivity measurement and tensile test specimens. Thermal conductivity was measured based on the laser flash method. The structure of the composite was also investigated by fracture surface observation after tensile testing. It is revealed that two types of fillers were composited with PA6 to obtain higher thermal conductivity than that of a single filler with the same filler content. This is because the different shapes of the two fillers made the thermally conductive path.

Purpose: To assess the utility of measurement of the computed tomography (CT) attenuation value (CTav) in predicting tumor necrosis in hepatocellular carcinoma (HCC) patients who achieve a complete response (CR), defined using modified Response Evaluation Criteria in Solid Tumors (mRECIST), after lenvatinib treatment. Method: We compared CTav in arterial phase CT images with postoperative histopathology in four patients who underwent HCC resection after lenvatinib treatment, to determine CTav thresholds indicative of histological necrosis (N-CTav). Next, we confirmed the accuracy of the determined N-CTav in 15 cases with histopathologically proven necrosis in surgical specimens. Furthermore, the percentage of the tumor with N-CTav, i.e., the N-CTav occupancy rate, assessed using Image J software in 30 tumors in 12 patients with CR out of 571 HCC patients treated with lenvatinib, and its correlation with local recurrence following CR were examined. Results: Receiver operating characteristic (ROC) curve analysis revealed an optimal cut-off value of CTav of 30.2 HU, with 90.0% specificity and 65.0% sensitivity in discriminating between pathologically identified necrosis and degeneration, with a CTav of less than 30.2 HU indicating necrosis after lenvatinib treatment (N30-CTav). Furthermore, the optimal cut-off value of 30.6% for the N30-CTav occupancy rate by ROC analysis was a significant indicator of local recurrence following CR with 76.9% specificity and sensitivity (area under the ROC curve; 0.939), with the CR group with high N30-CTav occupancy (≥30.6%) after lenvatinib treatment showing significantly lower local recurrence (8.3% at 1 year) compared with the low (p < 0.001, 61.5% at 1 year). Conclusion: The cut-off value of 30.2 HU for CTav (N30-CTav) might be appropriate for identifying post-lenvatinib necrosis in HCC, and an N30-CTav occupancy rate of >30.6% might be a predictor of maintenance of CR. Use of these indicators have the potential to impact systemic chemotherapy for HCC.

Abstract Background Transarterial chemoembolization (TACE) is the standard treatment for intermediate stage hepatocellular carcinoma (HCC) (Barcelona Clinic Liver Cancer [BCLC] B). However, it often leads to a poor prognosis and decreased hepatic function especially in patients with BCLC substage B2. Lenvatinib (LEN) was demonstrated to be efficacious in these patients in the REFLECT phase 3 trial. We therefore aimed to evaluate the efficacy and safety of LEN as a first-line treatment for the patients with HCC at BCLC substage B2. Methods This prospective observational study used LEN in TACE-naïve patients with HCC at BCLC substage B2 and preserved hepatic function. The primary endpoint was overall survival. A one-year survival rate threshold of 60% and an expected survival rate of 78%, based on previous reports of TACE, was assumed for setting the sample size. With a one-sided α-type error of 5% and 70% detection power, 25 patients were required over a 2-year enrollment period and 10-month follow-up period. Results Thirty-one patients were enrolled in this study from June 2018 to June 2020. The 1-year survival rate was 71.0% (90% confidence interval, 68.4–73.6%). Median overall and progression-free survival periods were 17.0 and 10.4 months, and the objective response rates according to Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1 and modified RECIST criteria were 22.6% and 70.0%, respectively. Common adverse events (AEs) were fatigue (68%), hypertension (65%), anorexia (61%), palmar-plantar erythrodysesthesia (39%), and thrombocytopenia (32%) of any grade; aspartate aminotransferase increased (23%), alanine aminotransferase increased (16%), and grade ≥ 3 proteinuria (13%). Treatment interruption and dose reduction were required in 61% and 81% of patients, respectively. LEN was discontinued in 29 patients due to disease progression (n = 17), AEs (n = 9), conversion to curative treatments (n = 2), and sudden death (n = 1), whereas post-LEN treatments were administered in 18 patients, including systemic chemotherapy (n = 11), TACE (n = 6), transarterial infusion (n = 1) and clinical trial (n = 1). Conclusions The results suggest that LEN provides treatment benefits as an initial therapeutic in patients with BCLC substage B2 HCC with a safety profile comparable to that previously reported.

Introduction: The aim of this study was to clarify whether magnetic resonance angiography (MRA)-based road mapping of the para-aortic transfemoral access route can reduce the procedural time of mechanical thrombectomy in patients with acute ischemic stroke. We further investigated the role of pre-procedural MRA-based road mapping in optimal initial catheter selection for rapid mechanical thrombectomy. Materials and Methods: We retrospectively reviewed 57 consecutive patients with acute ischemic stroke who underwent mechanical thrombectomy at our hospital between April 2018 and May 2021. Twenty-nine patients underwent MRA-based road mapping to visualize the para-aortic access route, whereas 28 patients only underwent routine head magnetic resonance imaging/angiography without MRA-based road mapping before neuro-interventional procedures. We then compared the basic procedural times required for mechanical thrombectomy, such as the time from femoral artery puncture to recanalization (“puncture to recanalization time”) and the time from the admission to recanalization (“door to recanalization time”), between the groups. Results: MRA-based road mapping significantly reduced the “puncture to recanalization time” (52.0 min vs. 70.0 min; p = 0.019) and the “door to recanalization time” (146 min vs. 183 min; p = 0.013). Conclusion: MRA-based road mapping of the para-aortic access route is useful to reduce the procedural time of mechanical thrombectomy in acute stroke patients, possibly by enabling optimal initial catheter selection during the procedure.

Abstract Background Although second‐line treatment for pancreatic cancer has been proven to have survival benefit, it is not clear which is the most preferred regimen. This study compared the efficacy and safety of modified FOLFIRINOX (mFOLFIRINOX) and sequential chemotherapy (FOLFIRI/FOLFOX) as a second‐line treatment regimen for unresectable pancreatic cancer. Method This was a retrospective single‐center analysis of all patients who initiated treatment with mFOLFIRINOX or sequential chemotherapy from December 2014 to May 2019 as a second‐line treatment for unresectable pancreatic cancer. The sequential chemotherapy group included all patients who initiated sequential chemotherapy. For efficacy analysis, the primary endpoint was overall survival (OS) of all patients, excluding those with locally advanced pancreatic cancer. For safety analysis, we assessed the incidence of grade ≥3 adverse events in all patients. Results Seventy‐four patients (mFOLFIRINOX group, n = 44; sequential chemotherapy group, n = 30) were included. OS tended to be slightly prolonged in the mFOLFIRINOX group than in the sequential chemotherapy group (median 10.6 [95% confidence interval {CI} 5.9–13.8] vs. 8.5 [95% CI 5.0–12.2] months; hazard ratio 1.40 [95% CI 0.71–2.71]). The objective response rate and disease control rate were 8.1% and 64.9%, respectively, in the mFOLFIRINOX group and 3.8% and 42.3%, respectively, in the sequential chemotherapy group. In safety analysis, the grade ≥3 rates of neutropenia, febrile neutropenia, and anorexia were 40.9%, 6.8%, and 18.2%, respectively, in the mFOLFIRINOX group and 3.3%, 0%, and 3.3%, respectively, in the sequential chemotherapy group. Conclusions Whereas efficacy tended to be slightly better in the mFOLFIRINOX group than in the sequential chemotherapy group, given the higher incidence of grade ≥3 adverse events with mFOLFIRINOX than with sequential chemotherapy, sequential chemotherapy is a regimen with better risk–benefit balance than mFOLFIRINOX, and can be considered a second‐line treatment option for patients with unresectable pancreatic cancer.

The feature extraction of human activity recognition (HAR) based on sensor data has been studied as a hand-crafted method. The significant feature extraction ability is a key factor in improving the accuracy of HAR. Recently, deep learning methods have been employed for feature extraction. In this paper, we review previous studies on deep learning methods in HAR and discuss suitable models for feature extraction. First, we applied various convolutional neural networks to clarify the effective architecture for HAR. Afterward, we developed advanced models by embedding submodules, such as self-attention and recurrent neural networks, often adopted in recent studies. Comparative experiments on HASC, UCI, and WISDM public datasets showed that Inception-V3, which used cross-channel multi-size convolution transformation, outperformed other backbones. Through comparative experiments after embedding submodules, submodules do not always have a positive effect on accuracy. Compared with other submodules, SENet has a positive effect. We conclude that it is essential to select an appropriate backbone model before applying the submodules, and submodules are unnecessary in some cases.

In this study, we proposed a new fabrication method of artificial bone materials using Ceramic Injection Molding (CIM) and verified the mechanical properties of the fabricated compacts. Since ceramic parts can be machined in the green parts from CIM, it is possible to manufacture custom-made artificial bones that match the defective parts. The porosity of sintered compacts affected cell growth. Thus, powder loading, binder composition, and content were changed for controlling the porosity of sintered compacts. As a result, it was confirmed that porosity and mechanical properties were controlled. Bending strength slightly decreased with increasing porosity, however, it is enough for artificial bone.

Purpose: To evaluate the feasibility of renal artery-based segmentation of kidneys with renal cell carcinoma (RCC), based on three-dimensional (3D) software for the simulation of segmental artery clamping (SAC), and to correlate it with RENAL nephrometry score. Methods: Fifty RCCs (< 4 cm) identified from a pathological database search between January 2015 and January 2018 were included retrospectively. On computed tomography (CT) images, the relevant kidney, tumor, and renal artery were annotated semi-automatically on the commercial workstation, and renal artery-based segmentation was performed using 3D Voronoi diagrams. Simulation of SAC was performed by a radiologist and urologist in consensus. The volume of the whole kidney and tumor and estimated rescued volume for possible SAC cases were calculated. The correlation between possible SAC and RENAL nephrometry score was investigated. The reproducibility of the calculation of each volume and the interrater reliability of SAC simulation were assessed. Results: In the anatomical analysis, 44 patients had a single main renal artery and six had two main renal arteries, and of these, an early division pattern was observed in 11 cases. In the 3D simulation software, 22 out of 50 cases (44 %) were determined as possible SAC. The agreement of the SAC simulation was excellent (kappa = 0.96). RENAL nephrometry score was significantly different in the anterior/posterior and exophytic/endophytic components between possible and impossible SAC groups. Conclusions: Renal artery-based segmentation of kidneys with RCC on CT images using 3D simulation software is feasible for effectively estimating the possibility of SAC with high reproducibility.

Abstract The purpose was to assess whether consecutive monitoring of oxygenation by photoacoustic imaging (PAI) can objectively predict intestinal viability during surgery for acute mesenteric ischemia (AMI). PAI uses laser light to detect relative amounts of oxygenated and deoxygenated hemoglobin in intestinal tissue. In 30 rats, AMI was induced by clamping the mesenteric and marginal vessels of the ileum for 0 min in the control group, 30 min in the mild group, and 180 min in the severe group (10 rats per group). After 60 min of reperfusion, intestinal damage was evaluated pathologically. Oxygenation of the intestine was monitored throughout the procedure in real time by a commercially available PAI system and compared among the groups. All rats showed irreversible (i.e. transmucosal or transmural infarction) damage in the severe group. After reperfusion, the oxygenation in the mild group recovered immediately and was significantly higher than in the severe group at 1, 5, 10, 30, and 60 min (P = .011, 002,

Abstract Background Malignant gastric outlet obstruction (MGOO) occasionally occurs due to pancreaticobiliary cancer. Endoscopic duodenal stenting (DS) is a common treatment for MGOO. However, it has been reported that DS does not have sufficient patency time for it to be used in patients who have a potentially increased lifespan. Nowadays, systemic chemotherapy for pancreaticobiliary cancer has developed, and its anti-tumour effect would make time to stent dysfunction longer. Therefore, we retrospectively evaluated the association between objective response to systemic chemotherapy, followed by DS and time to stent dysfunction in patients with advanced pancreaticobiliary cancer. Methods This retrospective study included 109 patients with advanced pancreaticobiliary cancer who received systemic chemotherapy after DS. Patients who showed complete or partial response were defined as responders. The rest were defined as non-responders. Time to stent dysfunction was compared between responders and non-responders using the landmark analysis at 2 months after DS. Death without recurrence of MGOO was considered as a competing risk for time to stent dysfunction. Results Combination and monotherapy regimens were adopted for 46 and 63 patients, respectively. Median progression-free survival and overall survival were 3.2 months (95% confidence interval [CI], 2.4–4.0) and 6.0 months (95% CI, 4.6–7.3). Objective response was observed in 21 patients (19.3%). Median time to stent dysfunction was 12.5 months (95% CI, 8.4–16.5) in the entire cohort. In 89 patients, responders had a lower cumulative incidence of stent dysfunction than non-responders: 9.5 and 19.1% at 6 months, and 19.0 and 27.9% at 1-year, respectively. There was difference of time to stent dysfunction between responders and non-responders among patients who received combination regimen as the first-line treatment with p-value of 0.009: cumulative incidence was 0 and 42.9% at 6 months, and 9.3 and 57.1% at 1-year, respectively. Conclusions Longer time to stent dysfunction is expected when systemic chemotherapy following DS suppresses tumour progression; DS is slated to be a standard treatment for MGOO even in patients with pancreaticobiliary cancer and a long lifespan.

Abstract Background Undifferentiated carcinoma (UC) of the pancreas is a rare subtype of pancreatic cancer. Although UC has been considered a highly aggressive malignancy, no clinical studies have addressed the efficacy of chemotherapy for unresectable UC. Therefore, we conducted multicenter retrospective study to investigate the efficacy of chemotherapy in patients with UC of the pancreas. Methods This multicenter retrospective cohort study was conducted at 17 institutions in Japan between January 2007 and December 2017. A total of 50 patients treated with chemotherapy were analyzed. Results The median overall survival (OS) in UC patients treated with chemotherapy was 4.08 months. The details of first-line chemotherapy were as follows: gemcitabine (n = 24), S-1 (n = 12), gemcitabine plus nab-paclitaxel (n = 6), and other treatment (n = 8). The median progression-free survival (PFS) was 1.61 months in the gemcitabine group, 2.96 months in the S-1 group, and 4.60 months in the gemcitabine plus nab-paclitaxel group. Gemcitabine plus nab-paclitaxel significantly improved PFS compared with gemcitabine (p = 0.014). The objective response rate (ORR) was 4.2% in the gemcitabine group, 0.0% in the S-1 group, and 33.3% in the gemcitabine plus nab-paclitaxel group. Gemcitabine plus nab-paclitaxel also showed a significantly higher ORR compared with both gemcitabine and S-1 (gemcitabine plus nab-paclitaxel vs. gemcitabine: p = 0.033; gemcitabine plus nab-paclitaxel vs. S-1: p = 0.034). A paclitaxel-containing first-line regimen significantly improved OS compared with a non-paclitaxel-containing regimen (6.94 months vs. 3.75 months, respectively; p = 0.041). After adjustment, use of a paclitaxel-containing regimen in any line was still an independent predictor of OS (hazard ratio for OS, 0.221; 95% confidence interval, 0.076–0.647; p = 0.006) in multiple imputation by chained equation. Conclusions The results of the present study indicate that a paclitaxel-containing regimen would offer relatively longer survival, and it is considered a reasonable option for treating patients with unresectable UC.

Previous genome-wide association studies have identified risk loci for pancreatic cancer but were centered on individuals of European ancestry. Here the authors identify GP2 gene variants associated with pancreatic cancer susceptibility in populations of East Asian ancestry.

Abstract Background Coil-assisted retrograde transvenous obliteration (CARTO) is a modified balloon-occluded retrograde transvenous obliteration (BRTO) technique using coils instead of an indwelling balloon. A method involving two microcatheter systems forming a double access route has been reported. We report a case of CARTO using a steerable microcatheter to successfully treat gastric varices (GV). Case presentation A 79-year-old man was admitted for treatment of intractable GV due to liver cirrhosis. The GV were drained mainly into the left inferior phrenic vein, not the usual gastrorenal shunt. Introducing the balloon catheter to the left inferior phrenic vein was difficult due to mild stenosis between the inferior vena cava and inferior phrenic vein and the shunt angle. A CARTO technique was performed with 5% ethanolamine oleate with iopamidol from a single access route by inverting the steerable microcatheter distal to the coil placement site. Conclusion CARTO has advantages in cases where performing BRTO is difficult. Using a steerable microcatheter simplifies the procedure by reducing the required access routes in CARTO.

Abstract Background The relationship between the risk of right heart failure in primary acute pulmonary embolism after embolization and the residual thrombus sites in the pelvis and lower limbs is not clear. Methods This single‐center retrospective observational study examined the results of contrast‐enhanced computed tomography and venous ultrasonography of patients with primary acute PE and DVT. We assessed the association between the occurrence of right heart failure and age; gender; pulmonary thrombosis distribution; most proximal site of deep vein thrombosis in the soleal vein, inferior vena cava (IVC), or common iliac vein (CIV); DVT distribution; and malignancy using univariate and multivariate logistic regression. Results In all, 77 of 165 patients were male (mean age: 65.1 ± 13.7 years). Right heart failure occurred in 53 patients (32.1%). Multivariate analysis revealed that the odds ratio (OR) for right heart failure was significantly lower in patients with the most proximal site of DVT in the IVC/CIV (OR = 0.07, 95% confidence interval [CI] 0.01‐0.62, P = .017), while it was significantly higher in females (OR = 2.51, 95% CI 1.05‐6.01, P = .039), and in patients who exhibited the presence of bilateral venous thrombosis (OR = 3.89, 95% CI 1.60‐9.48, P = .003). Conclusion A significant factor involved in PE without right heart failure was the most proximal site of DVT in the IVC/CIV, and significant risk factors associated with PE with right heart failure were more prevalent in females and in patients who exhibited the presence of bilateral venous thrombosis.

Objectives In the arterial phase of gadoxetate disodium administration for dynamic MRI, transient severe motion (TSM) sometimes occurs, making image evaluation difficult. This study was to identify risk factors for TSM in a clinical study, and confirm them and investigate the cause in an animal study. Methods A retrospective, single-center, observational study included patients who underwent dynamic MRI using gadoxetate disodium for the first time from April 2016 to September 2019 and free-breathing MRI was performed. Differences in clinical characteristics and laboratory tests between the presence and absence of TSM were examined. Animal experiments were conducted in 50 rats; gadoxetate disodium was injected into three sites (distal inferior vena cava (IVC), ascending aorta, and descending aorta) to identify the organ which triggers respiratory irregularities. Phosphate-buffered saline and gadopentetate dimeglumine were also injected into the distal IVC. In addition, to evaluate the effect of albumin, gadoxetate disodium was diluted with phosphate-buffered saline or 5% human serum albumin and injected into the ascending aorta. The time course of the respiratory rate was monitored and evaluated. Results 20 of 51 (39.2%) patients showed TSM. On multivariable analysis, a low albumin level was an independent risk factor (P = .035). Gadoxetate disodium administration caused significant tachypnea compared to gadopentetate dimeglumine or PBS (an elevation of 16.6 vs 3.0 or 4.3 breaths/min; both P < .001) in rats. The starting time of tachypnea was earlier with injection into the ascending aorta than into the descending aorta (10.3 vs 17.9 sec; P < .001) and the distal IVC (vs 15.6 sec; P < .001). With dilution with albumin instead of phosphate-buffered saline, tachypnea was delayed and suppressed (9.9 vs 13.0 sec; P < .001, 24.1 vs 17.0 breaths/min; P = .031). Conclusions A low albumin level is a risk factor for TSM, which could be caused by the effect of gadoxetate disodium on the head and neck region.

The poly(lactic acid) (PLA)-tricalcium phosphate (TCP) composite attracts much attention as a material for a bone fixation device because both have bioabsorbability. However, the applications of the composite bone fixation device are limited to low-loaded regions because of lower strengths. In this study, PLA and TCP/PLA composite cylindrical billets were extruded to improve their strengths, with the aim of clarifying the molecular orientation behavior of the PLA and TCP/PLA billets in extrusion. First, the effect of the orientation behavior in the PLA billets on the extrusion ratio (ER) was calculated. Next, the TCP/PLA billets were analyzed. The molecular orientation obtained by extrusion was investigated by a combination of the finite element method and the chain network model. Consequently, the orientation function of the extruded billet was found to increase with the ER. Furthermore, the orientation function of the TCP/PLA billet was higher than that of the PLA billet, which may be due to the change in the yield stress and n value of the billet by TCP addition. The orientation distribution in the radius direction of the extruded PLA billet showed that the orientation function at the surface region was larger than that at the center region. This orientation distribution might be because the movement distance of the surface region during extrusion was longer than that in the center region. The surface region in the billet was drawn by the difference of those movement distances and might be orientated. The workability of the PLA and TCP/PLA billets was also investigated using pressure during extrusion. The results showed that the extrusion pressure increased with the TCP content and ER. Therefore, extrusion workability decreased with the TCP content and the ER.

Abstract Background The efficacy of hepatic arterial infusion chemotherapy (HAIC) for advanced hepatocellular carcinoma (HCC) remains unclear. We conducted a multi-center randomized phase II study comparing a sequential HAIC-sorafenib regimen versus sorafenib alone as an initial therapy for HCC. Methods Patients were randomly assigned (ratio, 1:1) to receive sequential HAIC with cisplatin followed by sorafenib (HAIC group, n = 35) or sorafenib alone (sorafenib group, n = 33) as an initial therapy. The primary endpoint was the one-year survival rate. Secondary endpoint included overall survival (OS), the 2-year survival rate, the time-to-progression (TTP), the objective response rate (ORR), the disease control rate (DCR), and safety. Results For the primary endpoint, the one-year survival rates were 46% in the HAIC group and 58% in the sorafenib group. The median OS period was 10.0 months (95% CI, 7.0–18.8) in the HAIC group and 15.2 months (95% CI, 8.2–19.7) in the sorafenib group (hazard ratio [HR], 1.08; 95% CI, 0.63 to 1.86, P = 0.78). The median TTP, ORR and DCR in the HAIC group were 2.8 months (95% CI, 1.7–5.5), 14.3, and 45.7%, respectively, while those in the sorafenib group were 3.9 months (95% CI, 2.3–6.8), 9.1, and 45.5%, respectively. No unexpected adverse events related to HAIC or sorafenib were observed in either group. Conclusions Sequential HAIC with cisplatin and sorafenib does not improve the survival benefit, compared with sorafenib alone, when used as an initial therapy for advanced HCC. However, this study was underpowered in regard to its primary and secondary endpoints, so the results should be interpreted with caution. Trial registration UMIN ID 000006147, registration data: August 11, 2011.

The Fist-Edge-Palm (FEP) task, a manual hand task, has been used to detect frontal dysfunctions in clinical situations: its performance failures are observed in various prefrontal cortex (PFC)-related disorders, including schizophrenia. However, previous imaging studies reported that the performance of the FEP task activated motor-related areas, but not the PFC. Here, we aimed to investigate the relationships between the performance of the FEP task and PFC functions. Hemodynamic activity in the PFC, including the dorsolateral PFC (area 46) and frontal pole (area 10), was recorded. Healthy young subjects performed the FEP task as well as a palm tapping (PT) task (control task) three times. The subjects also completed a Wisconsin Card Sorting Test (WCST) and Schizotypal Personality Scale (STA) questionnaire. We found that hemodynamic activity (Oxy-Hb) in the PFC increased in the first trial of the FEP task but decreased considerably in the second and third trials compared to the PT task. The number of performance errors in the FEP task also decreased in the second and third trials. Error reduction (i.e., learning) in the FEP task between the first and second trials was negatively correlated with schizotypal trait and the number of perseveration errors in the WCST. Furthermore, changes in the PFC hemodynamic activity between the first and second trials were positively correlated with error reduction in the FEP task between the first and second trials, and negatively correlated with the number of perseveration errors in the WCST. These results suggest that learning in the FEP task requires PFC activation, which is negatively associated with perseveration errors in the WCST. The results further suggest that the FEP task, in conjunction with near-infrared spectroscopy, may be useful as a diagnostic method for various disorders with PFC dysfunction.

In this study, we develop a method for detecting the motions performed on a trampoline using an accelerometer mounted on a smartwatch. This method will lead to a system that can be used to promote trampoline exercise using a home trampoline by detecting motions on the trampoline using a smartwatch. We proposed a method based on the convolutional neural network to detect the motions on a trampoline. As a result of the performance evaluation by leave-one-subject-out cross-validation on eight subjects, our method achieves 78.8% estimation accuracy, which is the best estimation accuracy compared to the baseline methods. We also evaluate the inference time and the battery consumption when the model is actually running on a smartwatch. Our method is effective for on-device prediction.

Sports prosthesis for lower-extremity amputees has a mechanical structure similar to flat springs, and its elastic energy is expected to improve sports performance. However, it is quite challenging to represent the mechanical phenomena during the takeoff action with sports prosthesis because the contact point to the ground moves based on the direction and deformation of the prosthesis. The purpose of this study is to propose a parametric model of sports prosthesis based on the flat spring design formulas to represent the deformation and rolling contact with the ground with a reasonable computational cost. The shape of the prosthesis is modeled as serial elements, and it can easily be changed by using design parameters, such as the curvature and length of each element. The curvature of each element of the prosthesis is modified by the deflection angle of the flat spring model, and the contact point to the ground is calculated by considering the deformation and rolling contact. The spring properties obtained from the proposed model well agreed with the result of a finite element analysis. Moreover, simulation results revealed that the deformed shape of the prosthesis and the takeoff action in the long jump qualitatively agreed with the actual phenomena. As future research, the proposed model, coupled with the human body model, will be applied to a computer simulation system to optimize the shape of the prosthesis in order to improve sports performance.

The mechanical properties of bio-absorbable plastics, which is used as a bon fixation, change in the body because the plastics is hydrolyzed under the body environment. Theoretical prediction of the bio-degradation process will be useful for the medical application of these materials. Thus, a simple analytical model to predict hydrolytic characteristics of polymeric materials is necessary. In this study, several samples of poly(lactic acid) with different initial molecular weights, crystallinity and sample sizes were immersed in a phosphate buffered solution and the changes in the molecular weight and crystallinity were investigated. Theoretical analyses on the variation of these properties were performed and the results were compared with the experimental data. It is clarified that the theoretical results have successfully predicted the bio-degradation process of poly(lactic acid).

Poly(lactic acid) (PLA) has attracted much attention for use in bone fixation devices, which are used for fracture treatment, because it degrades to nontoxic lactic acid through nonenzymatic hydrolytic degradation. However, the application of such device is limited to relatively low-load regions, because mechanical properties of PLA is poor than that of metal materials. The process of drawing PLA fibers has attracted much attention as an approach for improving the mechanical properties of PLA bone fixation devices. The mechanical properties and molecular orientation of drawn PLA fibers and films have been investigated. However, the optimization of drawing conditions in bulk processes in relation to bone fixation devices is difficult because a large number of potential drawing conditions exist. The purpose of this study was to analytically clarify molecular orientation behavior in drawn PLA billets. The molecular orientation obtained by extrusion in PLA billets was investigated using a combination of the finite element method (FEM) and a chain network model. As a result of the FEM, first principal plastic strain was generated, mainly in the tapered components during extrusion; this strain was in the axial direction of the rod. Radius strain distributions showed that strain in the center region was almost uniform, whereas strain peaked near the surface. The orientation function increased with extrusion ratio (ER), and the peak orientation function in the surface region increased with taper angle. Thus, the magnitude and distribution of the orientation function in extruded PLA billets may be controllable by ER and taper angle, respectively.

We propose fast phase-contrast cine magnetic resonance imaging (PC-cine MRI) to allow breath-hold acquisition, and we compared intracranial hemo- and hydrodynamic parameters obtained during breath holding between full inspiration and end expiration. On a 3.0 T MRI, using electrocardiogram (ECG)-synchronized fast PC-cine MRI with parallel imaging, rectangular field of view, and segmented k-space, we obtained velocity-mapped phase images at the mid-C2 level with different velocity encoding for transcranial blood flow and cerebrospinal-fluid (CSF) flow. Next, we calculated the peak-to-peak amplitudes of cerebral blood flow (ΔCBF), cerebral venous outflow, intracranial volume change, CSF pressure gradient (ΔPG), and intracranial compliance index. These parameters were compared between the proposed and conventional methods. Moreover, we compared these parameters between different utilized breath-hold maneuvers (inspiration, expiration, and free breathing). All parameters derived from the fast PC method agreed with those from the conventional method. The ΔPG was significantly higher during full inspiration breath holding than at the end of expiration and during free breathing. The proposed fast PC-cine MRI reduced scan time (within 30 s) with good agreement with conventional methods. The use of this method also makes it possible to assess the effects of respiration on intracranial hemo- and hydrodynamics.

In order to improve bioactivity of hydroxyapatite (HA), the surface of HA was modified with calcium or magnesium ion irradiation. Calcium ion irradiation improved bioactivity of HA up to ion dose 1014 ions/cm2, whereas magnesium ion irradiation did not affect bone-like apatite formation. It is found that this different phenomena were attributed to surface electrical potential. Ion irradiation generally induces surface nano-scopic damage, however the strength of HA was not significantly affected by ion irradiation. From cell proliferation, no toxicity of HA irradiated with calcium ions was confirmed. From these results, the effectiveness of calcium ion irradiation on the treatment of bone defect using HA is confirmed.

Poly(lactic acid) (PLA) has attracted much attention as a material for bioabsorbable bone fixation devices, however degradation rate of PLA is very low. Surface treatment of PLA has been investigated to increase degradation rate due to improvement in hydrophilicity. In this study, effects of ion-implantation on degradation rate and mechanical properties were investigated. Argon gas which is chemically stable was used as ion source, and argon ion was implanted in the surface of PLA. The contact angle and the surface roughness of the ion-implanted PLA were measured to evaluate hydrophilicity, and tensile tests and micro-indentation tests were conducted to evaluate mechanical properties. The difference in surface morphology after in vitro degradation test between ion-implanted and un-implanted region was observed to investigate degradation properties of ion-implanted PLA. As a result, tensile strength increased by 8.2 % compared to un-implanted specimen and Vickers hardness increased by 9.5%. The ion-implantation might affect mechanical properties in the overall specimen rather than those in the surface. The result of in vitro degradation test showed that an initial degradation rate was accelerated by ion-implantation. This result is consistent with the increasing hydrophilicity of ion-implanted PLA. Those results suggested that ion-implantation accelerates degradation of PLA without decreasing mechanical properties.

PURPOSE:To evaluate the utility of photoacoustic imaging in measuring changes in renal oxygen saturation after ischemia-induced acute kidney injury, and to compare these measurements with histological findings and serum levels of kidney function. MATERIAL AND METHODS:Acute kidney injury was induced by clamping the left renal pedicle in C57Bl/6 mice, with a 35-min ischemic period used to induce mild renal injury (14 mice) and a 50-min period for severe injury (13 mice). The oxygen saturation was measured before induction, and at 5 time-points over the first 48 h after induction, starting at 4 h after induction. Oxygen saturation, histological score, kidney volume, and the 24 h creatinine clearance rate and serum blood urea nitrogen were also measured on day 28. Between-group differences were evaluated using a Mann-Whitney U-test and Dunn's multiple comparisons. The association between oxygen saturation and measured variables was evaluated using Spearman's correlation. A receiver operator characteristic curve was constructed from oxygen saturation values at 24 h after heminephrectomy to predict chronic renal function. RESULTS:The oxygen saturation was higher in the mild than severe renal injury group at 24 h after induction (73.7% and 66.9%, respectively, P

Genome-wide association studies (GWASs) have identified many single nucleotide polymorphisms (SNPs) that are significantly associated with pancreatic cancer susceptibility. We sought to replicate the associations of 61 GWAS-identified SNPs at 42 loci with pancreatic cancer in Japanese and to develop a risk model for the identification of individuals at high risk for pancreatic cancer development in the general Japanese population. The model was based on data including directly determined or imputed SNP genotypes for 664 pancreatic cancer case and 664 age- and sex-matched control subjects. Stepwise logistic regression uncovered five GWAS-identified SNPs at five loci that also showed significant associations in our case-control cohort. These five SNPs were included in the risk model and also applied to calculation of the polygenic risk score (PRS). The area under the curve determined with the leave-one-out cross-validation method was 0.63 (95% confidence interval, 0.60-0.66) or 0.61 (0.58-0.64) for versions of the model that did or did not include cigarette smoking and family history of pancreatic cancer in addition to the five SNPs, respectively. Individuals in the lowest and highest quintiles for the PRS had odds ratios of 0.62 (0.42-0.91) and 1.98 (1.42-2.76), respectively, for pancreatic cancer development compared with those in the middle quintile. We have thus developed a risk model for pancreatic cancer that showed moderately good discriminatory ability with regard to differentiation of pancreatic cancer patients from control individuals. Our findings suggest the potential utility of a risk model that incorporates replicated GWAS-identified SNPs and established demographic or environmental factors for the identification of individuals at increased risk for pancreatic cancer development.

We have built a new isonucleoside derivative on a 2,6-dioxobicyclo[3.2.0]heptane skeleton as a potential anti-HIV agent. To synthesize the target compound, an acetal-protected dihydroxyacetone was first converted to a 2,3-epoxy-tetrahydrofuran derivative. Introduction of an azide group, followed by the formation of an oxetane ring, gave a pseudosugar derivative with a 2,6-dioxobicyclo[3.2.0]heptane skeleton. The desired isonucleoside was obtained by constructing a purine base moiety on the scaffold, followed by amination.

This paper presents a simple method for analyzing the monetary trade-off between rising airframe material cost and reduced jet fuel cost for supporting the decision-making in designing lightweight but expensive new materials. The method considers the weight growth factor, Breguet range equation, specific strength, material cost, fuel price, and aircraft range. A model analysis reveals that rising fuel price can drastically change the optimum airframe materials from legacy aluminum alloys to carbon fiber-reinforced plastics.

Poly(lactic acid) (PLA) attracts much attention as a typical biodegradable and biocompatible polymer, because it degrades to nontoxic lactic acid through non-enzymatic hydrolytic degradation. Processing of PLA bone fixation devices have been investigated to improve their mechanical properties. Among fixations, screws are referred as one of the most general bone fixation device. The purpose of the present study is to clarify the effect of initial higher-order structure on degradation behavior and associated mechanical properties for self-reinforced PLA screws. PLA screws were prepared through a series of routes including casting extrusion drawing and forging. These screws were immersed in phosphate buffer solution (PBS) for 0, 8, 16 and 24 weeks, and orientation function, crystallinity, molecular weight and shear strength were measured. As a result, initial shear strength increased and degradation ratio decreased with orientation. This is due to lower water absorption caused by orientation crystallization. Shear strength decreased approximately 15 % at least with 24 weeks immersion. The results of the crystallinity showed that the screws were selectively hydrolyzed in amorphous region. This fact suggested that shear strength retention depends on hydrolysis in amorphous region. Initial shear strength for extrusion ratio (ER) 2 is the highest although the orientation function is the lowest. And the strength rapidly decreased with 8 weeks immersion. This might be due to hydrolysis of oriented tie chains. Although β crystals emerged only at ER 4, there was not clear difference in molecular weights and shear strength. This result suggested that the crystal form has little effects on degradation behavior and mechanical properties.

BackgroundProton beam therapy (PBT) achieves good local control for hepatocellular carcinoma (HCC), and toxicity tends to be lower than for photon radiotherapy. Focal liver parenchymal damage in radiotherapy is described as the focal liver reaction (FLR); the threshold doses (TDs) for FLR in the background liver have been analyzed in stereotactic ablative body radiotherapy and brachytherapy. To develop a safer approach for PBT, both TD and liver volume changes are considered clinically important in predicting the extent of damage before treatment, and subsequently in reducing background liver damage. We investigated appearance time, TDs and volume changes regarding FLR after PBT for HCC.Material and methodsPatients who were treated using PBT and were followed up using gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (Gd-EOB-DTPA MRI) after PBT were enrolled. Sixty-eight lesions in 58 patients were eligible for analysis. MRI was acquired at the end of treatment, and at 1, 2, 3 and 6 months after PBT. We defined the FLR as a clearly depicted hypointense area on the hepatobiliary phase of Gd-EOB-DTPA MRI, and we monitored TDs and volume changes in the FLR area and the residual liver outside of the FLR area.ResultsFLR was depicted in all lesions at 3 months after PBT. In FLR expressed as the 2-Gy equivalent dose (α/β = 3 Gy), TDs did not differ significantly (27.0±6.4 CGE [10 fractions [Fr] vs. 30.5±7.3 CGE [20 Fr]). There were also no correlations between the TDs and clinical factors, and no significant differences between Child-Pugh A and B scores. The volume of the FLR area decreased and the residual liver volume increased, particularly during the initial 3 months.ConclusionThis study established the FLR dose for liver with HCC, which might be useful in the prediction of remnant liver volume for PBT.

In this study, effects of strain rate on the mechanical properties of injection-molded poly(L-lactide) (PLLA) were investigated experimentally. The effect of crystallinity on the strain rate dependency of mechanical properties of PLLA was also examined by annealing the specimens at 70 and 130 °C for 24 hours. In order to characterize the mechanical properties, tensile and compressive tests were conducted. The results of tensile tests indicate that the Young's modulus kept constant up to strain rate of 10-1. On the other hand, tensile strength of non-annealing, 70°C-24h and 130°C-24 specimens increased with increasing strain rates up to 10-1, 10-2 and 10-3, respectively, and decreased or kept constant because of decrease in the fracture strain with increasing strain rate. The effect of strain rate became lower with increasing crystallinity, which means the strain rate dependency of the PLLA under tensile loading is more effective in the amorphous region. The results of compressive tests indicate that the compressive Young's modulus kept constant up to strain rate of 10-1. On the other hand, 0.2 % proof stress increased with increasing strain rate. This tendency was similar to the tensile test.

PurposeTo assess the feasibility of texture analysis for classifying fibrosis stage and necroinflammatory activity grade in patients with chronic hepatitis C on T2-weighted (T2W), T1-weighted (T1W) and Gd-EOB-DTPA-enhanced hepatocyte-phase (EOB-HP) imaging.Materials and methodsFrom April 2008 to June 2012, MR images from 123 patients with pathologically proven chronic hepatitis C were retrospectively analyzed. Texture parameters derived from histogram, gradient, run-length matrix, co-occurrence matrix, autoregressive model and wavelet transform methods were estimated with imaging software. Fisher, probability of classification error and average correlation, and mutual information coefficients were used to extract subsets of optimized texture features. Linear discriminant analysis in combination with 1-nearest neighbor classifier (LDA/1-NN) was used for lesion classification. In compliance with the software requirement, classification was performed based on datasets from all patients, the patient group with necroinflammatory activity grade 1, and that with fibrosis stage 4, respectively.ResultsBased on all patient dataset, LDA/1-NN produced misclassification rates of 28.46%, 35.77% and 20.33% for fibrosis staging and 34.15%, 25.20% and 28.46% for necroinflammatory activity grading in T2W, T1W and EOB-HP images. In the patient group with necroinflammatory activity grade 1, LDA/1-NN yielded misclassification rates of 5.00%, 0% and 12.50% for fibrosis staging in T2W, T1W and EOB-HP images respectively. In the patient group with fibrosis stage 4, LDA/1-NN yielded misclassification rates of 5.88%, 12.94% and 11.76% for necroinflammatory activity grading in T2W, T1W and EOB-HP images respectively.ConclusionTexture quantitative parameters of MR images facilitate classification of the fibrosis stage as well as necroinflammatory activity grade in chronic hepatitis C, especially after categorizing the input dataset according to the activity or fibrosis degree in order to remove the interference between the fibrosis stage and necroinflammatory activity grade on texture features.

Fiber reinforced thermoplastic composites has poorer matrix resin impregnation to fiber reinforcements, because of extreme high viscosity of molten thermoplastics. Fabrication method of intermediate materials using micro-braiding technique has been developed to overcome these difficulties. In this study, resin impregnation behavior in textile composites fabricated by micro-braiding technique was investigated. In order to predict the impregnation behavior, a simple model was proposed based on the Darcy's law and the continuity equation. Textiles composite plates were fabricated under various fabrication conditions using micro-braided yarn and the resin impregnation behavior in fiber yarn was investigated experimentally. The impregnation in single-ply textile composites is improved compared with that of multi-ply composites because single-ply composites have flatter fiber yarns which result in shorter impregnation distance. The numerical predictions calculated by boundary element method are in good agreement with the experimental results. This result suggests the effectiveness of the analysis proposed.

One of the newest and most promising methods for treating intractable neuronal diseases and injures is the transplantation of ex vivo-expanded human neural stem/progenitor cells (NSPCs). Human NSPCs are selectively expanded as free-floating neurospheres in serum-free culture medium containing fibroblast growth factor 2 (FGF2) and/or epidermal growth factor (EGF); however, the culture conditions still need to be optimized for performance and cost before the method is used clinically. Here, to improve the NSPC culture method for clinical use, we used an ATP assay to screen the effects of various reagents on human NSPC proliferation. Human NSPCs responded to EGF, FGF2, and leukemia inhibitory factor (LIF) in a dose-dependent manner, and the minimum concentrations eliciting maximum effects were 10 ng/ml EGF, 10 ng/ml FGF2, and 5 ng/ml LIF. EGF and LIF were stable in culture medium without NSPCs, although FGF2 was degraded. In the presence of human NSPCs, however, FGF2 and LIF were both degraded very rapidly, to below the estimated minimum concentration on day 3, but EGF remained above the minimum concentration for 5 days. Adding supplemental doses of each growth factor during the incubation promoted human NSPC proliferation. Among other supplements, insulin and transferrin promoted human NSPC growth, but progesterone, putrescine, selenite, D-glucose, and lactate were not effective and were cytotoxic at higher concentrations. Supplementing with conditioned medium from human NSPCs significantly increased human NSPC proliferation, but using a high percentage of the medium had a negative effect. These findings suggest that human NSPC culture is regulated by a balance in the culture medium between decreasing growth factor levels and increasing positive or negative factors derived from the NSPCs. Thus, in designing culture conditions for human NSPCs, it is useful to take the individual properties of each factor into consideration.