Effects of an urban forest healing program on cancer-related fatigue in cancer survivors.

PURPOSE: This study aimed to examine the effects of an eight-session structured urban forest healing program for cancer survivors with fatigue. BACKGROUND: Cancer-related fatigue (CRF) is a complex and multifactorial common symptom among cancer survivors that limits quality of life (QoL). Although health benefits of forest healing on physiological, physical, and psychological aspect as well as on the immune system have been reported in many studies, there is limited evidence on the efficacy of specialized forest program for cancer survivors. METHOD: A single-blinded, pre-test and post-test control group clinical trial was conducted with -75 cancer survivors assigned to either the forest healing group or the control group. The intervention was an eight-session structured urban forest program provided at two urban forests with easy accessibility. Each session consists of three or four major activities based on six forest healing elements such as landscape, phytoncides, anions, sounds, sunlight, and oxygen. Complete data of the treatment-adherent sample (≥ 6 sessions) was used to examine whether sociodemographic, clinical, physiological (respiratory function, muscle strength, balance, 6-min walking test) and psychological (distress, mood state, sleep quality, QoL) characteristics at baseline moderated the intervention effect on fatigue severity at 9 weeks. RESULTS: Significant time-group interactions were observed muscle strength, balance, 6-min walking test, distress, fatigue, moods, and QoL. The mean difference in fatigue between pre- and post-forest healing program was 9.1 (95% CI 6.2 to 11.9), 11.9 (95% CI 7.6 to 16.1) in moods, and -93.9 (95% CI -123.9 to -64.0) in QoL, showing significant improvements in forest healing group, but no significant improvements in the control group. CONCLUSION: This study suggests that a forest healing program positively impacts the lives of cancer survivors, by addressing both physical and psychological challenges associated with CRF. TRIAL REGISTRATION NUMBER: KCT0008447 (Date of registration: May 19, 2023).

Digital Health Interventions for Adult Patients With Cancer Evaluated in Randomized Controlled Trials: Scoping Review.

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.

Furosemide Dose Changes Associated with Furosemide/Tolvaptan Combination Therapy in Patients with Cirrhosis.

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.

Risk factors for loss of skeletal muscle mass in patients with cirrhosis.

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 < 0. We evaluated the relationships between LSMM and baseline clinical characteristics in patients with liver cirrhosis. RESULTS: A total of 166 patients with cirrhosis were enrolled and, of these, 123 patients (74.1%) showed LSMM. Multivariate analysis confirmed that hepatic encephalopathy, Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA+ -M2BP) (≥1.86), age (≥60 years), and grip strength (<18 kg for women and <26 kg for men) were independent predictors of skeletal muscle decline (P = 0.042, odds ratio [OR] 8.997, 95% confidence interval [CI] 1.083-74.71; P = 0.023, OR 3.970, 95% CI 1.468-6.177; P = 0.037, OR 2.526, 95% CI 1.056-6.045; and P = 0.002, OR 3.970, 95% CI 1.691-9.322, respectively). CONCLUSIONS: Advanced age, low grip strength, hepatic encephalopathy, and high WFA+ -M2BP might be risk factors for LSMM in liver cirrhosis patients.

Wisteria floribunda agglutinin-positive human Mac-2 binding protein in decompensated cirrhosis.

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 < 0.0001). The respective cut-off index values for decompensated cirrhosis were estimated using receiver-operating characteristic curves for WFA+ -M2BP levels. Using a cut-off index value of 3.37 for WFA+ -M2BP, predicting decompensated cirrhosis had a sensitivity of 77.8% and a specificity of 86.7%. CONCLUSIONS: WFA+ -M2BP values were higher in patients with decompensated liver cirrhosis.

Close correlation between urinary sodium excretion and response to tolvaptan in liver cirrhosis patients with ascites.

AIM: To assess the correlation between response to tolvaptan and treatment-related factors in liver cirrhosis patients. METHODS: This single-center retrospective study was carried out at Shonan Kamakura General Hospital in Kanagawa, Japan, between October 2013 and September 2015. Forty-three liver cirrhosis patients (mean age, 65.7 years) with insufficient responses to conventional diuretics for at least 7 days were enrolled. All patients received oral tolvaptan (7.5 mg/day for 7 days) and guideline-directed medical therapy including sodium intake restrictions. A responder to tolvaptan was defined as a patient having a ≥2-kg decrease in body weight 1 week after commencing drug treatment, and a non-responder was defined as a patient not losing ≥2 kg in body weight 1 week after commencing treatment. We investigated the correlation of change in body weight for 1 week after drug administration compared to baseline clinical characteristics. RESULTS: The mean body weight change from the baseline on the final dosing day was -2.47 ± 3.34 kg (P < 0.0001). There were 20 (46.5%) responders to tolvaptan. Urinary sodium and volume excretion was higher in responders than in non-responders (108.2 ± 70.5 vs 42.6 ± 36.7, P = 0.0003; 1462.8 ± 625.7 vs 960.9 ± 600.6, P = 0.0073). Logistic regression analyses for responders to tolvaptan were carried out, and independent correlation of the responders was urinary sodium excretion (P = 0.0114; hazard ratio, 0.9418; 95% confidence interval, 0.8768-0.9896) in the multivariate analyses. CONCLUSION: In decompensated liver cirrhosis patients, urinary excretion sodium showed good correlation with tolvaptan response.

Effect of DA-8031, a novel oral compound for premature ejaculation, on male rat sexual behavior.

OBJECTIVES: DA-8031 is a potent and selective serotonin transporter inhibitor developed for the treatment of premature ejaculation. The aim of the present study was to investigate the effects of DA-8031 on male sexual behavior in a rat model. METHODS: Sexual behavior was examined after an acute oral administration of 10, 30 or 100 mg/kg of DA-8031 in copulation studies with female rats. Pharmacokinetic parameters were calculated after oral administration of DA-8031 at a dose level of 30 mg/kg. RESULTS: DA-8031 treatment produced a dose-dependent increase in ejaculation latency time and showed statistical significance at 30 and 100 mg/kg dosage levels compared with the vehicle (P < 0.05). In addition, DA-8031 treatment reduced the mean number of ejaculations in a dose-dependent manner. No changes in post-ejaculatory interval, numbers of mounts, intromissions or ejaculations were observed at any dose. In pharmacokinetic study, the blood concentration of DA-8031 peaked at 0.38 ± 0.14 h after oral administration, and then rapidly declined with a half-life of 1.79 ± 0.32 h. CONCLUSIONS: Treatment with DA-8031 delays the ejaculation latency time without affecting the initiation of mounting behavior or post-ejaculatory interval in rats. Furthermore, DA-8031 is rapidly absorbed and eliminated after oral administration in rats. These preclinical findings provide a clue for the clinical testing of DA-8031 as an "on-demand" agent for premature ejaculation.

The needs for digital health and eHeath literacy of cancer patients, caregivers, and healthcare providers: A multicenter, descriptive correlational study.

PURPOSE: Digital health is an indispensable tool, but its use depends on the eHealth literacy (eHL) of end-users. This study aimed to understand the need for digital health and eHL among cancer patients, caregivers, and healthcare providers and to identify differences in digital health needs related to the eHL of cancer patients. METHODS: A multicenter, descriptive correlational study was conducted and included a total of 209 patients, 150 caregivers and 150 healthcare providers. Digital health needs were identified, and eHL was measured using the Korean version of the eHealth Literacy Scale. Differences in digital health needs in relation to the eHL of patients were analyzed. RESULTS: The most necessary digital health functions among cancer patients and caregivers were 'information and education on symptom management after cancer treatment' and 'education on coping methods for each type of cancer' (87.1-94.0%). Healthcare providers reported the need for a digital health function for 'medication information' and assisting in 'medical appointments' (96.7-98.0%). The preferred types of digital health were telemonitoring, mobile services, and telemedicine by telephone (81.3-90.5%). The mean eHL score of the cancer patients was 28.84 ± 6.75. Differences existed in the need for digital health functions and preferences for digital health types between cancer patients with high and low eHL. CONCLUSIONS: Cancer patients and caregivers expressed strong needs for digital health that provide information and education about symptom management and coping with cancer. Digital health interventions for cancer care need to be developed to reflect the identified needs and preferences and eHL of end-users.

Serum growth differentiation factor 15 is a novel biomarker with high predictive capability for liver cancer occurrence in patients with MASLD regardless of liver fibrosis.

BACKGROUND AND AIMS: Although metabolic dysfunction-associated steatotic liver disease (MASLD) patients with a Fib-4 index >1.3 are recommended for fibrosis evaluation via elastography or biopsy, a more convenient method identifying high-risk populations requiring follow-up is needed. We explored the utility of serum levels of growth differentiation factor-15 (GDF15), a cell stress-responsive cytokine related to metabolic syndrome, for stratifying the risk of clinical events in MASLD patients. METHODS: Serum GDF15 levels were measured in 518 biopsy-performed MASLD patients, 216 MASLD patients for validation, and 361 health checkup recipients with MASLD. RESULTS: In the biopsy-MASLD cohort, multivariate analysis indicated that the serum GDF15 level was a risk factor for liver cancer, independent of the fibrosis stage or Fib-4 index. Using a GDF15 cutoff of 1.75 ng/mL based on the Youden index, high-GDF15 patients, regardless of fibrosis status, had a higher liver cancer incidence rate. While patients with a Fib-4 index <1.3 or low-GDF15 rarely developed liver cancer, high-GDF15 patients with a Fib-4 index >1.3 developed liver cancer and decompensated liver events at significantly higher rates and had poorer prognoses. In the validation cohort, high-GDF15 patients had significantly higher incidences of liver cancer and decompensated liver events and poorer prognoses than low-GDF15 patients, whether limited to high-Fib-4 patients. Among health checkup recipients with MASLD, 23.0% had a Fib-4 index >1.3, 2.7% had a Fib-4 index >1.3 and >1.75 ng/mL GDF15. CONCLUSIONS: Serum GDF15 is a biomarker for liver cancer with high predictive capability and is useful for identifying MASLD patients requiring regular surveillance.

Validation of the Korean Version of the Cancer Fatigue Scale in Patients with Cancer.

Cancer-related fatigue is a highly prevalent and distressing symptom that negatively affects the quality of life of patients in all stages of cancer, including survivors. The Cancer Fatigue Scale (CFS) is a 15-item multidimensional instrument with the potential to enhance comprehension of fatigue. This study aimed to translate the original English version of the CFS into Korean and establish the validity and reliability of the translated version. A cross-sectional descriptive design was used to translate and validate the CFS in Korean. Factor analyses were performed to understand and establish construct and convergent validity with the Brief Fatigue Inventory (BFI), Functional Assessment of Chronic Illness Therapy-Fatigue (FACT-F), and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30). The CFS demonstrated good internal consistency (Cronbach's alpha coefficient for all 15 items = 0.806); the Kaiser-Meyer-Olkin Measure of Sampling Adequacy was found to be 0.897, and Bartlett's test of sphericity was significant (p < 0.001). Moderate correlations were found between BFI, FACT-F, and EROTC QLQ-C30, indicating moderate validity. However, there were differences in factorial validity between the original scale and the Korean version, demonstrating a need for further testing in a homogenous population of cancer patients. The findings of this validation and reliability study showed that the Korean version of the CFS is a concise, reliable, feasible, and practical tool for evaluating the multidimensional aspects of cancer-related fatigue in patients with cancer.

Effects of digital self-management symptom interventions on symptom outcomes in adult cancer patients: A systematic review and meta-analysis.

PURPOSE: Digital self-management (SM) interventions targeting symptom relief have demonstrated positive as well as null outcomes, whereas no study has synthesized the effect of the interventions. In this study, we aimed to evaluate the effectiveness of digital SM symptom interventions on symptom outcomes in adult cancer patients. METHODS: A systematic review and meta-analysis based on the previous scoping review was conducted. Six databases (PubMed, CINAHL, Embase, the Cochrane Library, RISS [Korean], and KoreaMed [Korean]) were searched. Population was adult cancer patients. Intervention was SM interventions applying digital health tool targeting symptom management. Comparison was usual care, waitlist controls or active controls. The primary outcome was symptom burden, and the secondary outcomes were individual symptoms. RESULTS: Our meta-analysis of 32 randomized controlled trials (RCTs) including 7888 patients demonstrated that digital SM symptom interventions had a significant effect on reducing symptom burden (effect size [ES] = -0.230) and relieving pain (ES = -0.292), fatigue (ES = -0.417), anxiety (ES = -0.320), and depression (ES = -0.261). CONCLUSIONS: Digital SM interventions can improve symptom outcomes in adult cancer patients. Oncology nurses should be aware that digital SM interventions have demonstrated promising outcomes in cancer patient care.

A present from the forest: Focus group interviews on cancer survivors' forest experiences.

Objective: 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. Methods: 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. Results: 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. Conclusions: 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.

Microstructural Control Strategy Based on Optimizing Laser Powder Bed Fusion for Different Hastelloy X Powder Size.

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.

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.

Effects of the Antidiabetic Drugs Evogliptin and Sitagliptin on the Immune Function of CD26/DPP4 in Th1 Cells.

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.

Synergistic effect of the herbal mixture C5E on gemcitabine treatment in PANC­1 cells.

The present study aimed to determine the anticancer effect of the herbal mixture extract C5E in the pancreatic cancer cell line, PANC­1, 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 PANC­1 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 V­FITC/PI double staining and Hoechst 33342 staining, respectively. SP cells share similar characteristics to cancer stem­like 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 PANC­1 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 co­treatment, 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 co­treatment, 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 co­treatment with C5E and gemcitabine compared with the treatment with either C5E or gemcitabine alone. As the co­treatment with gemcitabine and C5E was more effective than each individual treatment, the present study suggested that the combined treatment may exhibit synergistic effects in PANC­1 cells.

A Study on the Mechanical Properties of an Automobile Part Additively Printed through Periodic Layer Rotation Strategies.

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.

Acceptability and accuracy of patient-reported outcome measures (PROMs) for surveillance of breathlessness in routine lung cancer care: A mixed-method study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 of < 2), 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. CONCLUSION: 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.

Relationship between response to lusutrombopag and splenic volume.

AIM: To assess the correlation between the efficacy of lusutrombopag and clinical characteristics in patients with chronic liver disease. METHODS: In this retrospective, multicenter study, which conducted at four locations in Japan, 50 thrombocytopenic patients with chronic liver disease were enrolled. All patients received oral lusutrombopag (3.0 mg/d for 7 d) for chronic liver disease. We assessed the increase in platelet count after the trial drug administration. A treatment response was defined as a platelet count ≥ 5 × 104/µL and an increased platelet count ≥ 2 × 104/µL from baseline after drug administration. We evaluated the response to lusutrombopag compared to baseline clinical characteristics in patients with chronic liver disease. RESULTS: The numbers of responders and non-responders were 40 (80.0%) and 10 (20.0%), respectively. The patients were divided into a responder and non-responder group, and we added factors that may correspond to successful treatment with lusutrombopag. Splenic volume and body weight were lower in the responder group than in the non-responder group. White blood cell count and hemoglobin level were higher in responders compared with non-responders. Using a logistic regression model to assess the relationship between response to lusutrombopag and clinical characteristics, multivariate analysis confirmed that splenic volume was an independent factor that predicted the response of platelet counts (P = 0.025; odds ratio = 11.2; 95% confidence interval: 1.354-103.0). Splenic volume negatively correlated to changes in platelet count (r = -0.524, P = 0.001). CONCLUSION: Splenic volume influences the change in platelet counts after administration of lusutrombopag in patients with chronic liver disease.

Effect of branched-chain amino acid supplements on muscle strength and muscle mass in patients with liver cirrhosis.

OBJECTIVE: The aim of this study was to assess the effect of branched-chain amino acid (BCAA) supplements on muscle strength and muscle mass in patients with liver cirrhosis. PATIENTS AND METHODS: We carried out a single-center, prospective study of adult cirrhotic patients receiving nutrition therapy at Shonan Kamakura General Hospital. A 28-day pretreatment observation period was followed by a 24-week treatment period. Patients who fulfilled the treatment criteria received one package of oral BCAA supplement powder twice a day and the response was evaluated. A responder to BCAA in muscle strength and muscle mass was defined as a patient with an increased skeletal muscle mass index and hand grip assessed 24 weeks after drug treatment commenced. RESULTS: Eighty-two patients fulfilled our criteria and completed the treatment. In terms of muscle strength, there were 59 (72.0%) responders to BCAA supplementation with a significant increase in hand grip from before treatment (22.2±6.3 kg) to after treatment (23.9±6.4 kg) (P<0.001). In terms of muscle mass, 36 (43.9%) patients responded to BCAA with a slight decrease in skeletal muscle mass index from before treatment (7.40±1.62) to after treatment (7.30±1.49) (P=0.333). CONCLUSION: BCAA supplementation improved low muscle strength in patients with chronic liver disease, but did not increase muscle mass during the treatment period.