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In chronic liver diseases (CLD), p53 is constitutively activated in hepatocytes due to various etiologies as viral infection, ethanol exposure, or lipid accumulation. This study was aimed to clarify the significance of p53 activation on the pathophysiology of CLDs. In Kras-mutant liver cancer model, murine double minute 2 (Mdm2), a negative regulator of p53, was specifically deleted in hepatocytes [Alb-Cre KrasLSL-G12D Mdm2fl/fl (LiKM; KrasG12D mutation and Mdm2 loss in the liver)]. Accumulation of p53 and upregulation of its downstream genes were observed in hepatocytes in LiKM mice. LiKM mice showed liver inflammation accompanied by hepatocyte apoptosis, senescence-associated secretory phenotype (SASP), and the emergence of hepatic progenitor cells (HPC). More importantly, Mdm2 deletion promoted non–cell autonomous development of liver tumors. Organoids generated from HPCs harbored tumor-formation ability when subcutaneously inoculated into NOD/Shi-scid/IL2Rγ (null) mice. Treatment with acyclic retinoid suppressed growth of HPCs in vitro and inhibited tumorigenesis in LiKM mice. All of the phenotypes in LiKM mice, including accelerated liver tumorigenesis, were negated by further deletion of p53 in hepatocytes (Alb-Cre KrasLSL-G12D Mdm2fl/fl p53fl/fl). Activation of hepatic p53 was noted in liver biopsy samples obtained from 182 patients with CLD, in comparison with 23 normal liver samples without background liver diseases. In patients with CLD, activity of hepatic p53 was positively correlated with the expression of apoptosis, SASP, HPC-associated genes and tumor incidence in the liver after biopsy. In conclusion, activation of hepatocyte p53 creates a microenvironment prone to tumor formation from HPCs. Optimization of p53 activity in hepatocytes is important to prevent patients with CLD from hepatocarcinogenesis. Significance: This study reveals that activation of p53 in hepatocytes promotes liver carcinogenesis derived from HPCs, which elucidates a paradoxical aspect of a tumor suppressor p53 and novel mechanism of liver carcinogenesis. See related commentary by Barton and Lozano, p. 2824

Laser-aided additive manufacturing is used for complex shapes and Ni-based superalloy parts. This study aimed to optimize the additive manufacturing process of Hastelloy X alloy to obtain its excellent mechanical properties without pores or cracks in the additively manufactured parts. The additively manufactured Hastelloy X was analyzed by comparing porosity, microstructure, and mechanical properties in as-built and post-heat treatment conditions. In addition, the pores existing inside the as-built specimen considerably decreased after the hot isostatic press (HIP) treatment. Furthermore, cell/columnar microstructures were observed owing to a fast cooling rate in the as-built condition. However, after heat treatment, dendrite structures disappeared, and recrystallized equiaxed grains were observed. The tensile test results showed that there was mechanical anisotropy along the vertical and horizontal directions, and as the microstructure changed to equiaxed grains after heat treatment, the mechanical anisotropy decreased, and the high-temperature properties improved.

Supplementary Figure from Constitutive Activation of the Tumor Suppressor p53 in Hepatocytes Paradoxically Promotes Non–Cell Autonomous Liver Carcinogenesis

In chronic liver diseases (CLD), p53 is constitutively activated in hepatocytes due to various etiologies as viral infection, ethanol exposure, or lipid accumulation. This study was aimed to clarify the significance of p53 activation on the pathophysiology of CLDs. In Kras-mutant liver cancer model, murine double minute 2 (Mdm2), a negative regulator of p53, was specifically deleted in hepatocytes [Alb-Cre KrasLSL-G12D Mdm2fl/fl (LiKM; KrasG12D mutation and Mdm2 loss in the liver)]. Accumulation of p53 and upregulation of its downstream genes were observed in hepatocytes in LiKM mice. LiKM mice showed liver inflammation accompanied by hepatocyte apoptosis, senescence-associated secretory phenotype (SASP), and the emergence of hepatic progenitor cells (HPC). More importantly, Mdm2 deletion promoted non–cell autonomous development of liver tumors. Organoids generated from HPCs harbored tumor-formation ability when subcutaneously inoculated into NOD/Shi-scid/IL2Rγ (null) mice. Treatment with acyclic retinoid suppressed growth of HPCs in vitro and inhibited tumorigenesis in LiKM mice. All of the phenotypes in LiKM mice, including accelerated liver tumorigenesis, were negated by further deletion of p53 in hepatocytes (Alb-Cre KrasLSL-G12D Mdm2fl/fl p53fl/fl). Activation of hepatic p53 was noted in liver biopsy samples obtained from 182 patients with CLD, in comparison with 23 normal liver samples without background liver diseases. In patients with CLD, activity of hepatic p53 was positively correlated with the expression of apoptosis, SASP, HPC-associated genes and tumor incidence in the liver after biopsy. In conclusion, activation of hepatocyte p53 creates a microenvironment prone to tumor formation from HPCs. Optimization of p53 activity in hepatocytes is important to prevent patients with CLD from hepatocarcinogenesis.Significance:This study reveals that activation of p53 in hepatocytes promotes liver carcinogenesis derived from HPCs, which elucidates a paradoxical aspect of a tumor suppressor p53 and novel mechanism of liver carcinogenesis.See related commentary by Barton and Lozano, p. 2824

Supplementary Data from Constitutive Activation of the Tumor Suppressor p53 in Hepatocytes Paradoxically Promotes Non–Cell Autonomous Liver Carcinogenesis

This study aimed to investigate whether the antidiabetic drugs dipeptidyl peptidase 4 (DPP4) inhibitors such as evogliptin and sitagliptin affect the membrane DPP4 (mDPP4) enzymatic activity and immune function of T helper1 (Th1) cells in terms of cytokine expression and cell profiles. The mDPP4 enzymatic activity, cytokine expression, and cell profiles, including cell counts, cell viability, DNA synthesis, and apoptosis, were measured in pokeweed mitogen (PWM)-activated CD4+CD26+ H9 Th1 cells with or without the DPP4 inhibitors, evogliptin and sitagliptin. PWM treatment alone strongly stimulated the expression of mDPP4 and cytokines such as interleukin (IL)-2, IL-10, tumor necrosis factor-alpha, interferon-gamma, IL-13, and granulocyte-macrophage colony stimulating factor in the CD4+CD26+ H9 Th1 cells. Evogliptin or sitagliptin treatment potently inhibited mDPP4 activity in a dose-dependent manner but did not affect either the cytokine profile or cell viability in PWM-activated CD4+CD26+ H9 Th1 cells. These results suggest that, following immune stimulation, Th1 cell signaling pathways for cytokine expression function normally after treatment with evogliptin or sitagliptin, which efficiently inhibit mDPP4 enzymatic activity in Th1 cells.

Background Digital care has become an essential component of health care. Interventions for patients with cancer need to be effective and safe, and digital health interventions must adhere to the same requirements. Objective The purpose of this study was to identify currently available digital health interventions developed and evaluated in randomized controlled trials (RCTs) targeting adult patients with cancer. Methods A scoping review using the JBI methodology was conducted. The participants were adult patients with cancer, and the concept was digital health interventions. The context was open, and sources were limited to RCT effectiveness studies. The PubMed, CINAHL, Embase, Cochrane Library, Research Information Sharing Service, and KoreaMed databases were searched. Data were extracted and analyzed to achieve summarized results about the participants, types, functions, and outcomes of digital health interventions. Results A total of 231 studies were reviewed. Digital health interventions were used mostly at home (187/231, 81%), and the web-based intervention was the most frequently used intervention modality (116/231, 50.2%). Interventions consisting of multiple functional components were most frequently identified (69/231, 29.9%), followed by those with the self-manage function (67/231, 29%). Web-based interventions targeting symptoms with the self-manage and multiple functions and web-based interventions to treat cognitive function and fear of cancer recurrence consistently achieved positive outcomes. More studies supported the positive effects of web-based interventions to inform decision-making and knowledge. The effectiveness of digital health interventions targeting anxiety, depression, distress, fatigue, health-related quality of life or quality of life, pain, physical activity, and sleep was subject to their type and function. A relatively small number of digital health interventions specifically targeted older adults (6/231, 2.6%) or patients with advanced or metastatic cancer (22/231, 9.5%). Conclusions This scoping review summarized digital health interventions developed and evaluated in RCTs involving adult patients with cancer. Systematic reviews of the identified digital interventions are strongly recommended to integrate digital health interventions into clinical practice. The identified gaps in digital health interventions for cancer care need to be reflected in future digital health research.

Breathlessness in lung cancer negatively impacts on quality of life but often goes undetected and undertreated in clinical practice. There is a need for routine surveillance for early identification and proactive management of breathlessness using patient reported outcome measures (PROMs) in clinical care but it is unclear what PROMs should be used or are accurate for use in routine care.We used mixed-methods (quantitative surveys and qualitative interviews) to examine the predictors of breathlessness in 339 lung cancer participants and acceptability of PROMs. In addition to multivariate analysis to examine predictors of dyspnea, participants completed an acceptability survey and themes were derived for the qualitative data (n = 26) to explore patient experience of PROMs. We also tested the accuracy of PROMs using a Receiver Operating Characteristic and Area Under the Curve analysis.A total of 339 patients completed the breathlessness PROMs and acceptability survey and 26 patients participated in an in-depth interview to investigate their experiences of breathlessness and its PROMs. Prevalence of breathlessness was 51.9 % (n = 176) and 70.5 % of patients preferred the Medical Research Council (MRC) scale followed by the Breathlessness Intensity (BI) scale (63.7 %) among the five measures for breathlessness- Modified Borg Scale (MBS), Cancer Dyspnea Scale (CDS), MRC, BI, and Breathlessness Distress (BD). The finding showed wide variation in the MRC grades across the BI rating even among patients with the same BI score. AUC scores for the Borg scale was 0.71 (using MRC cut-off score of2), for CDS, 0.72, for BD, 0.70, and for BI 0.79. For an MRC score of 2, the Borg score cut-off was 0.8 (optimal sensitivity, 50 %; specificity, 93.3 %); the cut-off score of CDS, BD, BI score was 1.4 (optimal sensitivity, 67.1 %; specificity, 70 %), 1.5 (optimal sensitivity, 57.5 %; specificity, 73.3 %), and 1.5 (optimal sensitivity, 72.6 %; specificity, 83.3 %) respectively. AUC by ROC analysis for breathlessness and modest concordance among five PROMs showed important gaps between the individuals' experience and PROMs data. Three main themes from qualitative data included 1) Making sense of symptom reporting, 2) Valuing the reported data, 3) Managing the symptom of breathlessness.This study examined measurement of breathlessness using PROMs for routine clinical care and showed that severity measures alone do not accurately detect this symptomnor the experiential dimensions of breathlessness that are critical to guide appropriate intervention.

In additive manufacturing (AM), the powder properties and laser powder bed fusion (LPBF) process parameters influence the quality of materials and building parts. However, the relationship between the size of the powder, LPBF process parameters, and mechanical properties is not well-established. In addition, Hastelloy X (HX) is attracting attention for its excellent high-temperature properties, but it is difficult to process, such as by cutting and milling, because of its high hardness and high ductility. This can be overcome by applying the AM process. We compared the LPBF window process maps for two HX powders of different sizes. Despite their small difference of 19.7% in particle size, it was confirmed that the difference in laser power was more than 40 W, the difference in scan speed was more than 100 mm/s, and the difference in energy density was more than 20% under the optimal process conditions. The as-built specimen had a larger molten-pool size as the energy density was higher, which resulted in the differences in mechanical properties at room temperature and high temperature (816 °C). We considered the control of the size of the powder to obtain the properties required for each temperature condition. The microstructures and mechanical properties of the as-built LPBF specimens were also investigated and compared with those of cast HX. Because of the rapid melting and solidification processes in LPBF, the as-built HX exhibited nano-sized dendrite structures and large internal strain energy. This resulted in the as-built LPBF exhibiting a higher room-temperature tensile strength than the cast material. Under high-temperature conditions, the grain boundary of the as-built LPBF acts as a sliding path, and the as-built LPBF HX showed significantly better high-temperature tensile strength characteristics than the cast HX.

In metal product manufacturing, additive manufacturing (AM) is a method that has the advantage of fabricating complex shapes and customized production, unlike existing machining methods. However, owing to the characteristics of the AM process, anisotropy of macrostructure occurs because of various causes such as the scan direction, melting, fusion, and cooling of the powdered material. The macrostructure anisotropy is realized from the scan direction, and when a single layer is stacked in one direction, it is expressed as orthogonal anisotropy. Here, the classical lamination theory is applied to simply calculate the individual orthotropic layers by superimposing them. Through this, the authors analyzed whether the mechanical properties of the product are isotropically expressed with a periodic layer rotation strategy. To determine if the mechanical properties can be reasonably considered to be isotropic, a shock absorber mount for a vehicle was manufactured by AM. The tensile and vibration test performed on the product was compared with the finite element analysis and experimental results. As a result of the comparison, it was confirmed that the macroscopically of the product was considered isotropic as the load-displacement diagram and the fracture location coincided, as well as the natural frequency and mode shape.

Background: Few data have demonstrated that the combination therapy comprising a natriuretic drug and an aquaretic drug has improved renal function compared with the conventional diuretic therapy of only a natriuretic drug in patients with cirrhosis. Objective: This study aimed to assess the influence to the renal function by furosemide dose reductions after administration of tolvaptan in cirrhotic ascites patients. Methods: A 2-center, open-label, randomized study with a 24-week treatment period was conducted in Japan. Patients who met the study’s criteria were randomized to a conventional therapy group or a combination therapy group in a 1:1 ratio. The combination therapy group received tolvaptan and reduced furosemide doses compared with those received before the study enrollment. The conventional therapy group continued with the original dosage regimens. We assessed the change in estimated glomerular filtration rate (eGFR) from baseline through the duration of the study in the 2 groups. Results: Twenty-nine patients were randomized to receive either the combination therapy group (n = 14) or the conventional therapy group (n= 15). The change in the furosemide dose from baseline was –35.2 ± 10.1 mg in the combination therapy group. After 24 weeks of treatment, significantly greater improvement in eGFR was observed in the combination therapy group (2.4 ± 0.4 mL/min 1.73 m2) compared with those in the conventional therapy group (–5.1 ± 1.2 mL/min 1.73 m2; p = 0.013). Conclusion: A combination therapy of tolvaptan and furosemide enabled furosemide dose reductions. Systematic reductions of the furosemide doses can lead to the improvement of renal function.

The most common screening techniques to diagnose a patient’s illness are blood collection and intravenous procedures. To find a collection or injection site, conventional blood collection support tools, such as latex tubing and buckle-type tourniquets, are generally used to compress the patient’s blood vessels. This conventional passive method has significant problems such as latex allergy, vulnerability to site contamination and potential bloodstream infection, and physical damage due to improper use. To overcome the disadvantages of conventional blood collection support tools, an automatic tourniquet with a high-elasticity biocompatible strap was constructed. The automatic tourniquet is designed to automatically adjust the strap length using a motor to control the pressure according to the body dimensions of patients. In order to evaluate the performance of the automatic tourniquet, blood flow characteristics were analyzed using an ultrasound measurement system. The results demonstrated that the automatic tourniquet showed better performance compared with those of other blood collection support tools.

To explore cancer survivors' forest experiences and to understand the relevance of these experiences from their perspectives in the context of the growing interest in nature's impact on health and quality of life.From July 29 to August 12, 2021, four focus group interviews were conducted with cancer survivors who visited forests in South Korea. The data were analyzed using qualitative content and thematic analysis.The participants were 21 female cancer survivors with a mean age of 58.4 (age range 44-69) years. The focus group interviews revealed three themes and 10 sub-themes regarding subjective perceptions and experiences related to forests. The overarching themes were as follows: (1) awakened bodily senses and fascination with the forest; (2) remedial effect; and (3) a source of inspiration. These three themes capture the impact of forest experiences on participants' lives and the value they derived from these experiences. The participants considered these experiences a gift from forests. In particular, they experienced aesthetic enrichment and restorative effects such as boosted energy levels, reduced fatigue, and a buffer against mood swings. Finally, forests were a source of inspiration that led the participants toward personal growth.By gaining a better understanding of survivors' forest experiences, we identified that forest-based interventions for supportive cancer care can align with patients' values and preferences and serve as a secure space where they can feel cared for. This study can contribute to the development of forest-based interventions for cancer survivorship care.

AIM The present study aimed to assess the correlation between loss of skeletal muscle mass (LSMM) and the clinical characteristics of patients with liver cirrhosis. METHODS This multicenter, prospective study was undertaken at five locations in Japan and involved a 12-month observation period. After baseline assessment, the change in the skeletal muscle index per year (ΔSMI/y) was evaluated in the enrolled patients; LSMM was defined as ΔSMI/y

The present study aimed to determine the anticancer effect of the herbal mixture extract C5E in the pancreatic cancer cell line, PANC‑1, in the absence or presence of gemcitabine treatment, a chemotherapeutic drug used for the treatment of pancreatic cancer. The anticancer effects of C5E, gemcitabine and C5E plus gemcitabine in PANC‑1 cells following 72 h of treatment were investigated. The effect of each treatment on cell cycle arrest, apoptosis and the proportion of side population (SP) cells was determined using flow cytometric analysis following propidium iodide (PI), Annexin V‑FITC/PI double staining and Hoechst 33342 staining, respectively. SP cells share similar characteristics to cancer stem‑like cells, and a reduction in the SP is considered to be indicative of an anticancer effect. The percentage of SP cells and the cell viability of general PANC‑1 cells were significantly decreased in response to all treatments. The percentage of SP cells was reduced from 8.2% (control) to 3.9, 7.2 and 5.1% following the treatment with C5E, gemcitabine and the co‑treatment, respectively. All three treatments were discovered to inhibit cell viability by arresting the cell cycle at the S phase and promoted cell death by inducing early apoptosis, with the levels of apoptosis being increased from 1.9% (control) to 7.3, 2.5 and 12.0% following the treatment with C5E, gemcitabine and the co‑treatment, respectively. The mRNA expression levels of sonic hedgehog, which is implicated in the development of certain types of cancer, were downregulated to a greater extent following the co‑treatment with C5E and gemcitabine compared with the treatment with either C5E or gemcitabine alone. As the co‑treatment with gemcitabine and C5E was more effective than each individual treatment, the present study suggested that the combined treatment may exhibit synergistic effects in PANC‑1 cells.

BACKGROUND AND AIM An assay for Wisteria floribunda agglutinin-positive human Mac-2 binding protein (WFA+ -M2BP) has been reported as a useful non-invasive marker for the evaluation of the staging of fibrosis in several chronic liver diseases. However, available data on the effect of WFA+ -M2BP level in decompensated cirrhosis patients were limited. It is important that these investigations can validate the diagnostic utility of WFA+ -M2BP in the full range of patients with liver cirrhosis. METHODS A multicenter study was conducted at five locations in Japan. A total of 207 patients with liver cirrhosis were enrolled in the present study. To determine whether or not the WFA+ -M2BP value was associated with a progression of fibrosis among cirrhosis, this study examined WFA+ -M2BP levels between patients with cirrhosis in the decompensated and compensated groups. RESULTS The numbers and proportions of compensated and decompensated patients were 113 (54.6%) and 94 (45.4%), respectively. The average WFA+ -M2BP levels were 2.22 ± 1.61 in the compensated group and 6.91 ± 5.04 in the decompensated group. Significantly higher WFA+ -M2BP levels were observed in the decompensated group than those in the compensated group (P

The manufacturing industry nowadays has a greater interest in reducing global warming and promoting energy-saving measures than ever before. This has led to the development of eco-friendly manufacturing systems to replace conventional ones. Additive manufacturing (AM) technology, for instance, is expected to contribute to reducing material costs and energy consumption. Unlike conventional material-cutting manufacturing processes, AM enables designs of any shape in manufacturing by adding the necessary parts layer by layer. Direct energy deposition (DED) is one of the many AM technologies available for a variety of commercial steel powders such as P20, P21, SUS420, H13, D2 and other Non-ferrous metal powders. The DED is process that can be applied to various industries, like molding, medicine, and defense. Of these, its application to the molding industry is the most practical, since the process can be used to deposit different materials on existing parts. Using this technology, it becomes possible to manufacture high-functioning parts composed of various materials at reasonable cost. In this study, the DED is used to develop a high-performance and environmentally friendly trimming die. In this study, to develop a high performance and environmentally friendly trimming die using DED, evaluation of mechanical properties of material developed, stress analysis in shear work. The commercialization of the developed technology was evaluated and the commercial application of the developed technology was discussed.

An 83-year-old man was admitted with a chief complaint of exacerbation of dyspnea. His blood oxygen saturation was 90% in the recumbent position despite oxygen therapy, and it dropped to less than 80% when the patient attempted to sit upright. A computed tomography scan revealed a giant hepatic cyst compressing the right atrium and the inferior vena cava. After percutaneous drainage, the oxygen saturation improved and did not change with alteration of the patient's positions from recumbent to sitting or standing. This case report describes a patient with the platypnea-orthodeoxia syndrome due to a giant hepatic cyst successfully managed by percutaneous drainage.

Among the many additive manufacturing technologies, the directed energy deposition (DED) process has attracted significant attention because of the application of metal products. Metal deposited by the DED process has different properties than wrought metal because of the rapid solidification rate, the high thermal gradient between the deposited metal and substrate, etc. Additionally, many operating parameters, such as laser power, beam diameter, traverse speed, and powder mass flow rate, must be considered since the characteristics of the deposited metal are affected by the operating parameters. In the present study, the effect of energy input on the characteristics of H13 and D2 steels deposited by a direct metal tooling process based on the DED process was investigated. In particular, we report that the hardness of the deposited H13 and D2 steels decreased with increasing energy input, which we discuss by considering microstructural observations and thermodynamics.

Additive manufacturing (AM) has recently been receiving global attention. As an innovative alternative to existing manufacturing technologies, AM can produce three-dimensional objects from various materials. In the manufacturing industry, AM improves production cost, time, and quality in comparison to existing methods. In addition, AM is applied in the fabrication and production of objects in diverse fields. In particular, metal AM has been continuously commercialized in high value-added industries such as aerospace and health care by many research and development projects. However, the applicability of metal AM to the mold and die industry and other low value-added industries is limited because AM is not as economical as current manufacturing technologies. Therefore, this paper proposes an effective solution to the problem. This study examines a method for using direct energy deposition and heterogeneous materials, a heterogeneous material additive-manufacturing process for metals used to optimize the cooling channels and a key process in manufacturing hot-stamping dies. The improvements in the cooling performances and uniform cooling were evaluated by heat-flow analysis in a continuous process. Finally, trial products were fabricated using the proposed method, and a trial for hot stamping was conducted to examine the possibility of it being used in commercial applications.

The directed energy deposition process has been mainly applied to re-work and the restoration of damaged steel. Differences in material properties between the base and the newly deposited materials are unavoidable, which may affect the mechanical properties and durability of the part. We investigated the effect of heat treatment on the characteristics of tool steel deposited by the DED process. We prepared general tool steel materials of H13 and D2 that were deposited onto heat-treated substrates of H13 and D2, respectively, using a direct metal tooling process. The hardness and microstructure of the deposited steel before and after heat treatment were investigated. The hardness of the deposited H13 steel was higher than that of wrought H13 steel substrate, while that of the deposited D2 was lower than that of wrought D2. The evolution of the microstructures by deposition and heat treatment varied depending on the materials. In particular, the microstructure of the deposited D2 steel after heat treatment consisted of fine carbides in tempered martensite and it is expected that the deposited D2 steel will have isotropic properties and high hardness after heat treatment.

After the US government declared 3D printing technology a next-generation manufacturing technology, there have been many practical studies conducted to expand 3D printing technology to manufacturing technologies, called AMERICA MAKES. In particular, the Keck Center, located at the University of Texas at El Paso, has studied techniques for easily combing the 3D stacking process with space mobility and expanded these techniques to simultaneous staking techniques for multiple materials. Additionally, it developed convergence manufacturing techniques, such as direct inking techniques, in order to produce a module structure that combines electronic circuits and components, such as CUBESET. However, in these studies, it is impossible to develop a unified system using traditional independent through simple sequencing connections. This is because there are many problems in the integration between the stacking modeling of 3D printers and post-machining, such as thermal deformations, the precision accuracy of 3D printers, and independently driven coordinate problems among process systems. Therefore, in this paper, the integration method is suggested, which combines these 3D printers and subsequent machining process systems through an Internet-based cloud. Additionally, the sequential integrated system of a 3D printer, an NC milling machine, machine vision, and direct inking are realized.

The Direct Metal Tooling (DMT) process is a kind of additive manufacturing processes, which is developed using various commercial steel powders, such as P20, P21, SUS420, and other non-ferrous metal powders. The DMT process is a versatile process that can be applied to various fields, such as the molding industry, the medical industry, and the defense industry. Among them, the application of the DMT process to the molding industry is one of its most attractive and practical applications, since the conformal cooling channel cores of injection molds can be fabricated at a slightly expensive cost by using the hybrid fabrication method of DMT technology compared with parts fabricated with machining technology. The main objectives of this study are to provide various characteristics of the parts made using the DMT process compared with the same parts machined from bulk materials and evaluate the performance of the injection mold equipped with a conformal cooling channel core fabricated using the hybrid method of the DMT process.

In this paper, 433/865MHz dual band antenna is proposed by using IFA structure of a PCB antenna, the performance was improved by changing of the space between the feed point and short strip, varying the gap between the radiator and the ground plane and adding the branch line in the proposed antenna. To confirm the characteristics of the antenna parameters, HFSS from ANSYS Inc. was used for the analysis. RFID frequency band of ISO-18000-7 is 433MHz and EU-RFID frequency band of ISO-18000-6 is from 865.5 to 867.5MHz. Each of the 433/865MHz bandwidth of the proposed antenna is 5.2MHz and 18.2MHz. The maximum 433MHz antenna gain is -5.74dBi, the maximum 865MHz antenna gain is -3.36dBi. The Jig size of the proposed antenna is 60×44×1mm and the size of the antenna area 44×21mm. The results proved the possibility of the practical use on 433/865MHz by using the IFA structure that came from comparing and analyzing the measured and simulated data of the antenna. Key Words : IFA structure, 433/865MHz, Antenna, Dual band, Return Loss

An assay for Wisteria floribunda agglutinin-positive human Mac-2 binding protein (WFAA multicenter study was conducted at five locations in Japan. A total of 207 patients with liver cirrhosis were enrolled in the present study. To determine whether or not the WFAThe numbers and proportions of compensated and decompensated patients were 113 (54.6%) and 94 (45.4%), respectively. The average WFAWFA

Introduction and aim. We assessed the characteristics of virological response to a combination treatment of ombitasvir, paritaprevir, and ritonavir in hepatitis C virus genotype 1-infected elderly Japanese patients. Material and Methods. This multicenter prospective study was conducted at six locations in Japan. Seventy patients with chronic hepatitis C virus genotype 1b infection were orally administered ombitasvir/paritaprevir/ritonavir once daily for 12 weeks. The primary endpoint was the proportion of elderly patients with sustained virological response (SVR) 12 weeks after the completion of treatment. Adverse events were also recorded to evaluate drug safety and tolerability during the trial period. SVR in elderly patients (age > 65; 94% [47 / 50]) was lower than that in younger patients (100% [20 / 20]). Results. No significant differences in SVR 12 weeks after the completion of treatment were observed between the age groups (P = 0.153). Adverse events were observed in 16 patients (23.3%). Multivariate analysis confirmed that the change or discontinuation of concomitant drugs owing to drug interactions was independent of risk factors for adverse events associated with this drug combination (P = 0.015; odds ratio, 15.9; 95% confidence interval, 1.79 - 148). Ombitasvir/paritaprevir/ritonavir combination treatment was highly effective in elderly patients. Conclusion. Tolerability should be monitored in older patients for whom concomitant medications are discontinued or changed because of drug interactions.

AIM To assess the effects of a combination therapy with natriuretic and aquaretic drugs in cirrhotic ascites patients. METHODS A two-center, randomized, open-label, prospective study was conducted. Japanese patients who met the criteria were randomized to trial group and the combination diuretic group (received 7.5 mg of tolvaptan) or the conventional diuretic group (received 40 mg of furosemide) for 7 d in addition to the natriuretic drug which was used prior to enrolment in this study. The primary endpoint was the change in body weight from the baseline. Vital signs, fluid intake, and laboratory and urinary data were assessed to determine the pharmacological effects after administration of aquaretic and natriuretic drugs. RESULTS A total of 56 patients were randomized to receive either tolvaptan (n = 28) or furosemide (n = 28). In the combination and conventional diuretic groups, the average decrease in body weight from the baseline was 3.21 ± 3.17 kg (P < 0.0001) and 1.75 ± 2.36 kg (P = 0.0006), respectively, when measured on the final dosing day. Following 1 wk of treatment, a significantly greater reduction in body weight was observed in the combination diuretic group compared to that in the conventional diuretic group (P = 0.0412). CONCLUSION Compared to a conventional diuretic therapy with only a natriuretic drug, a combination diuretic therapy with natriuretic and aquaretic drugs is more effective for patients with cirrhotic ascites.

The introduction of direct-acting antiviral agents (DAAs) for the treatment of chronic hepatitis C virus (HCV) infection in patients undergoing hemodialysis (HD) has improved sustained virological response (SVR) rates. Our aim was to assess the characteristics of the virological response to daclatasvir (DCV) and asunaprevir (ASV) combination therapy for HCV in HD patients. A multicenter prospective study was conducted at eight centers in Japan. Patients on HD with chronic genotype 1b HCV infections were orally administered DCV and ASV for 24 weeks at doses of a 60-mg capsule once daily and a 100-mg tablet twice daily, respectively. The primary endpoint of this trial was the proportion of patients with a sustained virological response at 24 weeks after the treatment ended (SVR24). We also investigated the characteristics associated with the virological response to combination therapy. Thirty patients were enrolled in this study, and the proportion that achieved an SVR24 after treatment was 83.3% (25/30). Virological failure was observed in 4 patients (13.3%). Two exhibited virological breakthrough at weeks 16 and 20 of drug administration, and viral relapse occurred in 2 patients at weeks 4 and 8 after the end of treatment. Virological failure was defined as HCV-RNA levels exceeding 5.5 log10 IU/mL, and resistance-associated variants (RAVs) NS5A-L31M/V and Y93H were not exhibited at baseline. DCV and ASV therapy for chronic HCV on HD was significantly effective. Most importantly, patients with the low viral loads undergoing HD demonstrated a higher response to combination therapy regardless of RAV. UMIN Clinical Trials Registry UMIN000016181

Pancreatic cancer is the fourth leading cause of cancer death. Gemcitabine is widely used as a chemotherapeutic agent for the treatment of pancreatic cancer, but the prognosis is still poor. Berberine, an isoquinoline alkaloid extracted from a variety of natural herbs, possesses a variety of pharmacological properties including anticancer effects. In this study, we investigated the anticancer effects of berberine and compared its use with that of gemcitabine in the pancreatic cancer cell lines PANC-1 and MIA-PaCa2. Berberine inhibited cell growth in a dose-dependent manner by inducing cell cycle arrest and apoptosis. After berberine treatment, the G1 phase of PANC-1 cells increased by 10% compared to control cells, and the G1 phase of MIA-PaCa2 cells was increased by 2%. Whereas gemcitabine exerts antiproliferation effects through S-phase arrest, our results showed that berberine inhibited proliferation by inducing G1-phase arrest. Berberine-induced apoptosis of PANC-1 and MIA-PaCa2 cells increased by 7 and 2% compared to control cells, respectively. Notably, berberine had a greater apoptotic effect in PANC-1 cells than gemcitabine. Upon treatment of PANC-1 and MIA-PaCa2 with berberine at a half-maximal inhibitory concentration (IC50), apoptosis was induced by a mechanism that involved the production of reactive oxygen species (ROS) rather than caspase 3/7 activation. Our findings showed that berberine had anti-cancer effects and may be an effective drug for pancreatic cancer chemotherapy.