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Abstract There is insufficient evidence comparing the outcomes of tacrolimus-based remission induction therapy with infliximab in refractory ulcerative colitis (UC) and evidence regarding optimal strategies after tacrolimus-based remission induction therapy. We conducted a multi-institutional retrospective study of patients with UC treated with tacrolimus or infliximab between January 2010 and March 2019. The proportion of clinical remission at week 8 and cumulative colectomy-free rate were examined using propensity score matching analysis. The predictors for colectomy after tacrolimus induction were also investigated. Ninety patients in the tacrolimus group and 151 in the infliximab group were enrolled. The proportion of patients in clinical remission at week 8 was 65.2% in the matched tacrolimus group and 37.3% in the matched infliximab group (P = 0.0016), and the long-term colectomy-free rate was lower in the matched tacrolimus group than in the matched infliximab group (P = 0.0003). After clinical remission with tacrolimus, a serum albumin level of ≤ 3.5 g/dL at week 8 was extracted as a factor predicting colectomy (area under the curve: 0.94). Tacrolimus showed a higher remission induction effect for UC compared to infliximab. However, a high rate of colectomy after transition to maintenance treatment was found to be a concern for tacrolimus therapy.

Purpose: Currently, there is limited information regarding the utilization of pin-less augmented reality (AR) assistance in total hip arthroplasty (THA). This preliminary study aimed to evaluate the precision of acetabular cup placement in THA utilizing the AR Navigation “Pin-less” System (Pin-less AR navigation, prototype). Methods: A total of 72 consecutive primary THAs in 58 patients were categorized into two groups: the Pin-less AR navigation group and the conventional group. All THAs were conducted via the direct anterior approach. First, the absolute value of difference between the intra-operative and post-operative angles (absolute difference) was calculated in the Pin-less AR navigation group. Second, the absolute value of error between the post-operative angles and the target angles (absolute target error) was assessed both in the Pin-less AR navigation group and the conventional group. Results: The absolute difference in inclination and anteversion angles was 2.2 ​± ​1.4° and 2.4 ​± ​1.5°, respectively. The absolute target error in the Pin-less AR navigation group versus the conventional group was 1.9 ​± ​1.5° versus 4.2 ​± ​2.7° in inclination (P ​

Purpose: Conflicting evidence exists about the appropriate intra-operative soft tissue balance in posterior-stabilized (PS) total knee arthroplasty (TKA). The purpose of this prospective observational study was to investigate the impact of intra-operative soft tissue balance on post-operative knee flexion angle. Methods: A single surgeon performed 164 TKAs using a single brand of PS prosthesis via the subvastus approach without using a pneumatic tourniquet. Intra-operative soft tissue balance was quantified as the gaps between the femoral component and tibial osteotomy surface with the knee flexed at 0°, 30°, 90°, and 120° with the patellofemoral joint reduced. Multiple regression analyses were employed to identify independent predictors of knee flexion angle 1 year after TKA. Result: The pre-operative knee flexion angle and the gap difference between 120° and 0° flexion were positively correlated with knee flexion angle 1 year after TKA [β ​= ​0.37, 95% confidence interval (CI) 0.26–0.48, P ​

Purpose: Despite its clinical benefits, intraoperative navigation is currently used only in approximately 20% of total hip arthroplasties (THA) partly due to the high cost of the systems and time-consuming preoperative preparation. By providing a simpler and less expensive alternative, the use of intraoperative navigation is likely to increase among surgeons. In this study, we sought to validate the accuracy and utility of Fluoro HIP, a newly developed cup angle measurement software that runs on iOS devices. Methods: Twenty-seven patients who underwent primary total hip arthroplasty between June and September 2022 were included in the study. All patients underwent surgery in the supine position. Inclination and anteversion angles were determined using Fluoro HIP software based on the fluoroscopic images captured during surgery. Navigation errors were calculated by comparing with the values obtained from postoperative CT images. Results: The inclination and anteversion angles measured were 38.7 ​± ​3.9 and 15.0 ​± ​3.1°, respectively. The absolute value errors were 2.7 ​± ​1.9 and 3.0 ​± ​2.1° for the inclination and anteversion, respectively. Although Fluoro HIP software-based system may not be as precise as the conventional CT-based or portable navigation systems, the intraoperative evaluation of the cup angles by this system was considered to have acceptable accuracy and reproducibility for most THA cases performed in the supine position. Most importantly, our system requires no preoperative preparation and is significantly less expensive than other types of navigation systems currently in use. Conclusion: The Fluoro HIP software-based system is a highly cost-effective and affordable alternative to the conventional navigation systems.

Background: An automated measurement system for the placement angles of acetabular cup in total hip arthroplasty prostheses was developed utilizing artificial intelligence (AI) algorithms. The AI-powered system enables immediate measurement by capturing an anteroposterior pelvic X-ray through a smartphone camera. Methods: While developing the AI-powered measurement system, we trained AI utilizing 100 labeled anteroposterior pelvic X-rays to recognize the hip joint and 483 labeled anteroposterior pelvic X-rays to identify anatomical landmarks and the acetabular cup. To validate the AI-powered system, we measured the acetabular cup placement angles of 126 unlabeled post-total hip arthroplasty anteroposterior pelvic X-rays with both the AI-powered system and conventional measurement methods and assessed the correlation between the 2 methods. Results: The Pearson’s correlation coefficients for the acetabular cup placement angles measured using the AI-powered system and conventional method were 0.88 (95% confidence interval, 0.84-0.92, P < .001) in inclination angle and 0.76 (95% confidence interval, 0.67-0.83, P < .001) in anteversion angle, respectively. Conclusions: Both inclination and anteversion angles measured using the AI-powered system showed a strong correlation with angles obtained through conventional methods.

Abstract Background and aim Various techniques for direct biopsy from gastrointestinal subepithelial tumors (SETs) have been reported, although no standard method has been established. A common feature of these techniques is the removal of overlaying mucosa to enable direct biopsies from the SETs. These methods have been synthesized under the collective term “unroofing technique”. We conducted a multicenter retrospective study to assess its efficacy and identify potential complications. Methods This study was conducted in 10 hospitals and involved all eligible patients who underwent unroofing techniques to obtain biopsies for gastrointestinal SETs between April 2015 and March 2021. The primary endpoint was the diagnostic accuracy of the unroofing technique, and the secondary endpoints were the incidence of adverse events and the factors contributing to the accurate diagnosis. Results The study included 61 patients with 61 gastrointestinal SETs. The median tumor size was 20 mm, and the median procedure time was 38 min, with 82% successful tumor exposure. The rate of pathological diagnosis was 72.1%. In 44 patients with a pathological diagnosis, two showed discrepancies with the postresection pathological diagnosis. No factors, including facility experience, organ, tumor size, or tumor exposure, significantly affected the diagnostic accuracy. There was one case of delayed bleeding and two cases of perforation. Conclusion The diagnostic yield of the unroofing technique was acceptable. The unroofing technique was beneficial regardless of institutional experience, organ, tumor size, or actual tumor exposure.

Abstract The outcomes of patients with elderly onset (EO) inflammatory bowel disease (IBD) treated with anti-tumor necrosis factor (TNF) remains uncertain. The present study evaluated the efficacy and safety of anti-TNF treatment for bio-naïve EO-IBD. Elderly patients were defined as those 60 years and older, and further divided into those with EO (Elderly-EO) and those with non-elderly onset (Elderly-NEO). A total of 432 bio-naïve patients were enrolled in this multicenter observational study, comprising 55 with Elderly-EO (12.7%), 25 with Elderly-NEO (5.8%), and 352 under age 60 (Non-elderly, 81.5%). After 52 weeks of anti-TNF treatment, clinical and steroid-free remission rates were significantly lower in Elderly-EO than in Non-elderly (37.7% and 60.8%; P = 0.001, and 35.9% and 57.8%; P = 0.003, respectively), and comparable between Elderly-NEO and Non-elderly. Multivariate analysis revealed that elderly onset was a significant factor for both clinical remission (OR, 0.49, 95% CI 0.25–0.96) and steroid-free remission (OR, 0.51, 95% CI 0.26–0.99) after 52 weeks of anti-TNF treatment. The rate of cumulative severe adverse events was significantly higher in Elderly-EO than in Non-elderly (P = 0.007), and comparable between Elderly-NEO and Non-elderly. In conclusion, anti-TNF treatment for bio-naïve EO-IBD may be less effective and raise safety concerns.

Abstract Background The efficacy and safety of bevacizumab-containing chemotherapy for patients with metastatic duodenal and jejunal adenocarcinoma (mDJA) are unclear. The present study aimed to evaluate the efficacy of bevacizumab and to explore immunohistochemical markers that can predict the efficacy of bevacizumab for patients with mDJA. Methods This multicentre study included patients with histologically confirmed small bowel adenocarcinoma who received palliative chemotherapy from 2008 to 2017 at 15 hospitals. Immunostaining was performed for vascular endothelial growth factor-A (VEGF-A), TP53, Ki67, β-catenin, CD10, MUC2, MUC5AC, MUC6, and mismatch repair proteins. Results A total of 74 patients were enrolled, including 65 patients with mDJA and 9 with metastatic ileal adenocarcinoma. Patients with mDJA who received platinum-based chemotherapy with bevacizumab as first-line treatment tended to have a longer progression-free survival and overall survival than those treated without bevacizumab (P = 0.075 and 0.077, respectively). Multivariate analysis extracted high VEGF-A expression as a factor prolonging progression-free survival (hazard ratio: 0.52, 95% confidence interval: 0.30–0.91). In mDJA patients with high VEGF-A expression, those who received platinum-based chemotherapy with bevacizumab as a first-line treatment had significantly longer progression-free survival and tended to have longer overall survival than those treated without bevacizumab (P = 0.025 and P = 0.056, respectively), whereas no differences were observed in mDJA patients with low VEGF-A expression. Conclusion Immunohistochemical expression of VEGF-A is a potentially useful biomarker for predicting the efficacy of bevacizumab-containing chemotherapy for patients with mDJA.

Background The mammalian Notch family ligands delta‐like 3 (DLL3) is reported to be a potential therapeutic target for large cell neuroendocrine carcinomas (LCNEC). The effect of DLL3 expression on LCNEC prognosis has not yet been elucidated. Methods We reviewed the medical records of 70 LCNEC patients undergoing surgical resection between 2001 and 2015 using a prospectively maintained database. We performed immunohistochemistry for DLL3 and investigated the correlation between the sensitivity of LCNEC to platinum‐based adjuvant chemotherapy. Results DLL3 expression was positive in 26 (37.1%) LCNEC patients. A total of 23 patients (32.9%) received platinum‐based adjuvant chemotherapy. Among patients with DLL3 expression‐positive tumors, no difference was found in the five‐year overall survival (OS) or recurrence‐free survival (RFS) between patients with and without adjuvant chemotherapy (surgery + chemotherapy vs. surgery alone, five‐year OS: 58.3% vs. 35.7% P = 0.36, five‐year RFS: 41.7% vs. 35.7% P = 0.74). In contrast, among patients with DLL3‐negative tumors, significantly greater five‐year OS and RFS rates were observed for patients with adjuvant chemotherapy than for those without it (surgery + chemotherapy vs. surgery alone: five‐year OS: 90.0% vs. 26.9% P

Background and Aim Hypothyroidism might play a crucial role in the pathogenesis of non‐alcoholic fatty liver disease (NAFLD). The association of subclinical hypothyroidism with NAFLD has been inconsistent. The relationship of NAFLD with thyroid function parameters and subclinical hypothyroidism was determined. Methods This cross‐sectional study included 70 patients with subclinical hypothyroidism and 70 controls with euthyroidism matched according to gender, age, and body mass index (BMI). NAFLD was diagnosed via abdominal ultrasonography. The association between NAFLD and subclinical hypothyroidism was analyzed. Results The prevalence of NAFLD was significantly higher in patients with subclinical hypothyroidism than in those with euthyroidism. Multivariate analysis showed that subclinical hypothyroidism was an independent risk factor of NAFLD adjusted by metabolic‐related factors, such as BMI, triglyceride, high‐density lipoprotein‐cholesterol, hypertension, and diabetes. Thyroid‐stimulating hormone (TSH) was an independent risk factor of NAFLD adjusted by the same metabolic‐related factors, but free thyroxine (FT4) was not a risk factor. The FIB‐4 index, a noninvasive marker of liver fibrosis was significantly higher in patients with subclinical hypothyroidism than in those with euthyroidism. Compared with patients with euthyroidism, the proportion of the FIB‐4 index ≥2.67 was significantly higher, and the proportion of the FIB‐4 index

Abstract Purpose To illustrate a surgical technique for augmented reality (AR)‐assisted unicompartmental knee arthroplasty (UKA) and report preliminary data. Methods We developed an AR‐based navigation system that enables the surgeon to see the tibial mechanical axis superimposed on the patient’s leg in addition to the tibial cutting angle. We measured the tibial resection angle in 11 UKAs using postoperative radiographs and calculated the absolute difference between preoperative target angle and postoperative measured angle. The target angle was determined for each patient: mean values were 0.7° ± 1.0° varus in coronal alignment and 5.3° ± 1.4° posterior slope in sagittal alignment. Results The angles measured on postoperative radiographs were 2.6° ± 1.2° varus in the coronal plane and 4.8° ± 2.5° posterior slope in the sagittal plane. The absolute differences between the target and measured angles were 1.9° ± 1.5° in coronal alignment and 2.6° ± 1.2° in sagittal alignment. No patients experienced complications, including surgical site infection and periprosthetic fracture. Conclusion The AR‐based portable navigation system may provide passable accuracy in terms of proximal tibial resection during UKA. Level of Evidence IV

Background:. An augmented reality (AR)-based navigation system allows visualization of the center of the femoral head and femoral mechanical axis superimposed on the surgical field during total knee arthroplasty (TKA) and may help surgeons to improve the accuracy of distal femoral resection. Methods:. First, we resected 10 femoral Sawbones specimens using the AR-based navigation system and performed computed tomography (CT) to measure the resection angle of the distal part of the femur. We calculated the absolute values of the differences between angles measured using CT images and angles displayed on the smartphone screen of the navigation system. Second, we measured coronal alignment using standing long-leg radiographs for 72 patients undergoing TKA and compared the error in the resection angle between TKA using the AR-based navigation system and that using a conventional intramedullary guide. Results:. In the experimental study, the absolute values of the differences between angles measured on CT images and angles displayed using the AR-based navigation system were 0.8° ± 0.5° (range, 0.3° to 1.9°) in the coronal plane and 0.6° ± 0.5° (range, 0.0° to 1.4°) in the sagittal plane. In the clinical study, the mean absolute value of the error in coronal alignment was significantly smaller in the AR-based navigation group than the intramedullary-guide group (1.1° ± 1.0° [range, 0.0° to 3.2°] compared with 2.2° ± 1.6° [range, 0.0° to 5.5°], respectively; 95% confidence interval, 0.5° to 1.8°; p < 0.001). Conclusions:. The AR-based navigation system may enable surgeons to perform distal femoral resection more accurately than with the conventional intramedullary guide during TKA. Clinical Relevance:. This study validates the use of AR technology to enhance the precision of bone resection in TKA.

Abstract Background The aim of this study was to identify subgroups with good or bad prognosis in patients with pulmonary large cell neuroendocrine carcinoma (LCNEC) based on immunostaining patterns with neuroendocrine markers and compare them with small cell lung carcinoma (SCLC). Methods From January 2001 to December 2017, of all patients with resected LCNEC and SCLC, we selected patients whose pathological tumor sizes were ≤30 mm in diameter (defined as small‐sized tumors) and who underwent complete resection with lymphadenectomy. We classified patients with small‐sized LCNEC (sLCNEC) into two subgroups based on immunostaining patterns with three neuroendocrine markers (chromogranin A, synaptophysin, and NCAM) and compared them to small‐sized SCLC (sSCLC). Results A total of 48 patients with sLCNEC and 39 patients with sSCLC were enrolled. Of 48 patients with sLCNEC, 21 were categorized as the small‐sized triple‐positive group (sTP), whose patients were positive for the three neuroendocrine markers, and 27 patients were categorized as the small‐sized nontriple‐positive group (sNTP), whose patients were not positive for all three neuroendocrine markers. The percentage of lymph node metastasis was significantly lower in sNTP than in sTP and sSCLC. There was no significant difference in overall survival, but recurrence‐free survival (RFS) and tumor‐specific survival (TSS) were significantly poorer in sTP and sSCLC than in sNTP. Multivariate analysis revealed sTP and sSCLC were independent prognostic factors for poorer RFS and TSS than those of sNTP. Conclusions The sNTP subgroup had a good prognosis and the sTP subgroup a poor prognosis. There were some similarities in clinicopathological features between sTP and sSCLC.

Abstract Background This pilot study was performed to examine the accuracy of the AR-KNEE system, an imageless navigation system using augmented reality (AR) technology for total knee arthroplasty. The AR-KNEE system enables the surgeon to view information from the navigation superimposed on the surgical field on a smartphone screen in real time. Methods Using the AR-KNEE system, one surgeon resected 10 tibial sawbones with viewing the tibial axis and aiming varus/valgus, posterior slope, internal/external rotation angles, and resection level superimposed on the surgical field. We performed computed tomography of the resected sawbones and measured the varus/valgus, posterior slope, and internal/external rotation angles using a designated computer software. The thickness of the resected bone was measured using digital calipers. Results The absolute differences between the values displayed on the smartphone screen and the measurement values for varus/valgus, posterior slope, internal/external rotation angles, and thickness of the resected bone were 0.5° ± 0.2°, 0.8° ± 0.9°, 1.8° ± 1.5°, and 0.6 mm ± 0.7 mm, respectively. Conclusions This pilot study using sawbones suggested that the AR-KNEE system may provide reliable accuracy for coronal, sagittal, and rotational alignment in tibial bone resection during total knee arthroplasty.

Background and study aims In patients receiving antithrombotic therapy, the risks of delayed bleeding after endoscopic procedures for gastrointestinal neoplasms become a major problem. Few reports have shown the effects of delayed bleeding in patients taking anticoagulants after colorectal endoscopic submucosal dissection (ESD). This study aimed to evaluate the delayed bleeding events after colorectal ESD in patients receiving anticoagulant therapy. Patients and methods We retrospectively analyzed 87 patients taking anticoagulants who underwent colorectal ESD from April 2012 to December 2017 at 13 Japanese institutions participating in the Osaka Gut Forum. Among these patients, warfarin users were managed with heparin bridge therapy (HBT), continued use of warfarin, a temporary switch to direct oral anticoagulation (DOAC), or withdrawal of warfarin, and DOAC users were managed with DOAC discontinuation with or without HBT. We investigated the occurrence rate of delayed bleeding and compared the rates between warfarin and DOAC users. Results The delayed bleeding rate was 17.2 % among all patients. The delayed bleeding rate was higher in DOAC users than in warfarin users (23.3 % vs. 11.4 %, P = 0.14), although no statistically significant difference was observed. In DOAC users, the delayed bleeding rates for dabigatran, rivaroxaban, apixaban, and edoxaban users appeared similar (30 %, 18.2 %, 22.2 %, and 25 %, respectively). The onset of delayed bleeding in both warfarin and DOAC users was late, averaging 6.9 and 9.4 days, respectively. Conclusions Among patients taking anticoagulants, the risk of delayed bleeding after colorectal ESD was relatively high and the onset of delayed bleeding was late.

Abstract The exploration of energization and radiation in geospace (ERG) satellite, nicknamed “Arase,” is the second satellite in a series of small scientific satellites created by the Institute of Space and Astronautical Science of the Japan Aerospace Exploration Agency. It was launched on December 20, 2016, by the Epsilon launch vehicle. The purpose of the ERG project is to investigate how high-energy (over MeV) electrons in the radiation belts surrounding Earth are generated and lost by monitoring the interactions between plasma waves and electrically charged particles. To measure these physical processes in situ, the ERG satellite traverses the heart of the radiation belts. The orbit of the ERG is highly elliptical and varies due to the perturbation force: the apogee altitude is approximately 32,200–32,300 km, and the perigee altitude is 340–440 km. In this study, we introduce the scientific background for this project and four major challenges that need to be addressed to effectively carry out this scientific mission with a small satellite: (1) dealing with harsh environmental conditions in orbit and electromagnetic compatibility issues, (2) spin attitude stabilization and avoiding excitation of the libration by flexible structures, (3) attaining an appropriate balance between the mission requirements and the limited resources of the small satellite, and (4) the adaptation and use of a flexible standardized bus. In this context, we describe the development process and the flight operations for the satellite, which is currently working as designed and obtaining excellent data in its mission.

A pneumatocele is a cystic change of the lung that is caused by a check valve in the bronchiole due to infection, trauma and positive-pressure ventilation. We herein report a case of pneumatocele triggered by using of continuous positive airway pressure (CPAP) for sleep apnea syndrome (SAS) after pulmonary resection. A 69-year-old man underwent right upper lobectomy for lung cancer and developed interstitial pneumonia (IP) 10th postoperative day (POD). He was treated with steroid pulse therapy (solmedrol 500 mg × 3 days), and thereafter with oral steroid therapy (predonin 30mg/day). Well responded to the steroid therapy, IP was improved. However, he noticed bloody sputum 29th POD, and chest computed tomography showed a giant cystic lesion on the dorsal right lower lobe. We resected the cyst and the pathological findings revealed that the cystic lesion was pneumatocele, and CPAP was strongly suspected of triggering this disease.

BACKGROUND AND AIMS:Psychologic stress can affect the pathogenesis of inflammatory bowel disease (IBD), but the precise contribution of psychologic stress to IBD remains unclear. We investigated the association of psychologic stress with disease activity in patients with IBD, especially in terms of mental state and sleep condition. METHODS:This was a multi-center observational study comprising 20 institutions. Data were collected using survey forms for doctors and questionnaires for patients, and the association of psychologic stress with clinical parameters was investigated. Mental state was evaluated using the Center for Epidemiologic Studies Depression (CES-D) scale, and sleep condition was evaluated by querying patients about the severity of insomnia symptoms. RESULTS:A total of 1078 IBD patients were enrolled, including 303 patients with Crohn's disease and 775 patients with ulcerative colitis. Seventy-five percent of IBD patients believed that psychologic stress triggered an exacerbation of their disease (PSTE group) and 25% did not (non-PSTE group). The CES-D scores were significantly higher for patients with clinically active disease than for those in remission in the PSTE group (median (interquartile range) = 7 (4-9.5) vs. 5 (3-7), p < .0001), but not in the non-PSTE group (5 (2-8) vs. 4 (3-7), p = 0.78). Female sex and disease exacerbation by factors other than psychologic stress were independent factors of psychologic stress-triggered disease exacerbation. Also, patients with insomnia had higher disease activity than those without insomnia, especially in the PSTE group. CONCLUSIONS:A worsened mental state correlates with disease activity in IBD patients, especially those who believe that their disease is exacerbated by psychologic stress.

Background: This study aimed to compare the diagnostic performance of carbohydrate-deficient transferrin (CDT) and gamma-glutamyltranspeptidase (γ-GTP) to assess the single and combined benefits of these biological markers for the detection of chronic excessive alcohol consumption in patients with alcoholic cirrhosis. Methods: Biological markers were determined in blood samples from patients with alcoholic cirrhosis (drinking group, n = 35; nondrinking group, n = 81). The prediction accuracy of %CDT alone, γ-GTP alone, and their combination for the detection of excessive alcohol consumption was determined in patients with alcoholic cirrhosis. Results: Serum total bilirubin, alanine aminotransferase, aspartate aminotransferase, γ-GTP, and alkaline phosphatase levels and %CDT were significantly higher and serum albumin levels were significantly lower in the drinking group than in the nondrinking group. The combination of %CDT and γ-GTP compared with %CDT or γ-GTP alone showed a higher prediction accuracy. The combination of %CDT and γ-GTP exhibited a higher specificity than γ-GTP alone. However, in terms of sensitivity, no significant difference was found between single or combined markers. Conclusions: The combination of %CDT and γ-GTP is considered a useful biomarker of chronic excessive alcohol consumption in patients with alcoholic cirrhosis.

Molecular targeted therapy with lenvatinib is commonly offered to advanced hepatocellular carcinoma (HCC) patients, although it is often interrupted by adverse effects which require a reduction in the initial dose. Thus, an alternative lenvatinib-based therapy to compensate for dose reduction is anticipated. This study aimed to assess the effect of combination of low-dose of lenvatinib and the angiotensin-II (AT-II) receptor blocker losartan on human HCC cell growth. In vitro studies found that losartan suppressed the proliferation by inducing G1 arrest and caused apoptosis as indicated by the cleavage of caspase-3 in AT-II-stimulated HCC cell lines (Huh-7, HLE, and JHH-6). Losartan attenuated the AT-II-stimulated production of vascular endothelial growth factor-A (VEGF-A) and interleukin-8 and suppressed lenvatinib-mediated autocrine VEGF-A production in HCC cells. Moreover, it directly inhibited VEGF-mediated endothelial cell growth. Notably, the combination of lenvatinib and losartan augmented the cytostatic and angiostatic effects of the former at a low-dose, reaching those achieved with a conventional dose. Correspondingly, a HCC tumor xenograft assay showed that the oral administration of losartan combined with lenvatinib reduced the subcutaneous tumor burden and intratumor vascularization in BALB/c nude mice. These findings support that this regimen could be a viable option for patients intolerant to standard lenvatinib dosage.

This paper describes thermal performance of a small loop heat pipe device in an atmospheric condition. A comprehensive test program including start-up, power step up, power cycle and low power tests was performed. The effects of gravity on start-up and heat transport capability were also evaluated. An analytical model for the loop was developed to predict and evaluate the steady state operating performance. The test results demonstrated the robustness of the LHP. The analytical results showed good agreement with the test results except at the low power region. The feasibility of loop temperature control through compensation chamber temperature control was also experimentally demonstrated.

Loop Heat Pipes (LHPs) have been used in thermal control of spacecraft as next generation heat transport devices. Recently, multiple-evaporators LHP (MLHP) is under studied since the MLHP supplies autonomous thermal control function. However, some physical phenomena in the MLHP have not been clarified yet. The purpose of this study is to clarify thermal behavior of the MLHP under the microgravity. The MLHP used in this research has two evaporators and one condenser. Distilled water is used as the working fluid. 40W/40W, 80W/80W, 120W/0W, 0W/120W heat load were applied during the test. This experiment was conducted under microgravity for about 20 seconds, which was realized by parabolic flight. The vapor-liquid distribution in the wick core and the compensation chamber (CC) under the microgravity is presented. The effect of the microgravity for the working the MLHP is also discussed. The heat distributions in the MLHP when one and both evaporators were heated is also clarified

A lunar long duration method which utilizes a characteristic of a very low thermal conductivity of lunar regolith has been proposed. The principle of this method is to put heater in desired depth of the regolith and heat up the regolith layer during lunar daytime. Because of the very low thermal conductivity of regolith, stored heat in regolith propagates gradually and raises the surface temperature at cold lunar night. By this method, a lunar lander will be kept warm passively during cold lunar night. In this paper, a temporospatially small-scale experimental apparatus which simulate lunar surface environment was fabricated and thermal cycling condition and heater setting position was calculated by comparing lunar environment, and thermophysical properties of the lunar regolith and regolith simulant used in this work. The feasibility of a passive thermal control method with no electrical power during lunar night time was evaluated.

The effect of either adhesion or collagen molecules on cell attachment, insulin secretion, and glucose responsiveness was investigated in adult porcine pancreatic endocrine (PE) cells that were cultured for a longer term in vitro. Six different types of molecules—laminin, fibronectin, poly-L-lysine (PLL), type I collagen, gelatin, and Matrigel—were used. Approximately 2.0 × 105 cells per dish of each molecule type were cultured for 4 weeks. In the laminin group, the insulin accumulation was maintained at a significantly higher level than in the control group at 4 weeks of culture, and glucose-stimulated insulin secretion and the insulin-positive rate were also higher than in the control group. In the Matrigel group, islet-like cell clusters were formed, but insulin accumulation rapidly decreased at 3–4 weeks of culture. A large number of PE cells attached tightly and spread in the fibronectin group until the fourth week of culture, but their function was not better than those in the control group. In the PLL and gelatin groups, the PE cell function was not significantly different from that of the control group. In the type I collagen group, insulin secretion was inferior to that of the other groups. The results of this study suggest that laminin is the most suitable extracellular matrix for the long-term culture preservation of PE cells.

The effect of the synthetic extracellular matrix (ECM) in a diffusion chamber for a bioartificial endocrine pancreas (Bio-AEP) on pancreatic endocrine cells in vitro and its biocompatibility in dogs were investigated. Two different types of ECM were used: type I collagen treated with low antigen (type I LA), and reconstituted basement membrane matrix (Matrigel) derived from Englbreth-Holm-Swarm (EHS) mouse sarcoma. Matrigel contains growth and differentiation factors and cell adhesion molecules such as laminin, heparan sulfate proteoglycan, and entactin. Purified porcine pancreatic endocrine (PE) cells were suspended in type I LA or Matrigel and then placed into a 12-well culture plate (4 × 107 cells/ml · gel/well). The insulin accumulation from PE cells in Matrigel was significantly greater than that in type I LA (9.3 ± 3.6 mU/well vs. 2.3 ± 1.3 mU/well). When Bio-AEP with Matrigel and PE cells was implanted into the abdominal cavity of a pancreatectomized diabetic dog, the exogenous insulin requirement for maintaining normoglycemia was reduced for the first 4 weeks. However, after 6 weeks of implantation, fasting blood glucose levels suddenly increased. Laparotomy revealed encapsulated Bio-AEP with thick fibrous tissue. Following removal of the Bio-AEP from the abdominal cavity, another Bio-AEP containing type I LA and PE cells was implanted into the same dog. The exogenous insulin requirement was gradually decreased to almost half that of preim-plantation levels. Bio-AEPs containing type I LA or Matrigel, but not PE cells, were implanted into the abdominal cavities of four healthy dogs. After 4 weeks of implantation, the Bio-AEP with Matrigel was encapsulated with fibrous tissue similar to that in the diabetic dog, but the Bio-AEP with type I LA was not. These results indicate that Matrigel may be incompatible with dogs and that the type I LA is more suitable for Bio-AEP.