Seasonal influences on the efficacy of anti-programmed cell death (ligand) 1 inhibitors in lung cancer.

BACKGROUND: Seasonal variations in systemic immunity have been reported. This study aimed to evaluate whether seasonality affects the efficacy of anticancer immunotherapy. METHODS: A total of 604 patients with lung cancer receiving single anti-programmed cell death (ligand) 1 (anti-PD-[L]1) inhibitors from two prospective observational cohorts were screened. Primary outcomes were progression-free survival (PFS) and overall survival (OS). Patients were classified into two groups according to the season when the treatment started: winter (November-February) and other seasons (March-October). Kaplan-Meier analysis and Cox proportional hazards models were fitted to evaluate the impact of seasonality on survival. For validation, propensity score matching was performed. RESULTS: A total of 484 patients with advanced non-small cell lung cancer were included. In an unmatched population, multivariable analysis demonstrated that the winter group (n = 173) had a significantly lower risk of progression or death from immunotherapy than the other group (n = 311) (PFS: hazard ratio [HR], 0.77 [95% confidence interval (CI), 0.62-0.96]; p = .018; OS: HR, 0.77 [95% CI, 0.1-0.98]; p = .032). In a propensity score-matched population, the winter group (n = 162) showed significantly longer median PFS (2.8 months [95% CI, 1.9-4.1 months] vs. 2.0 months [95% CI, 1.4-2.7 months]; p = .009) than the other group (n = 162). The winter group's median OS was also significantly longer than that of the other group (13.4 months [95% CI, 10.2-18.0 months] vs. 8.0 months [95% CI, 3.6-8.7 months]; p = .012). The trend toward longer survival in the winter group continued in subgroup analyses. CONCLUSIONS: Starting an anti-PD-(L)1 inhibitor in winter was associated with better treatment outcomes in patients with lung cancer compared to other seasons.

Subjective Experience on Virtual Reality-Assisted Mental Health Promotion Program.

OBJECTIVE: Mental health promotion programs using virtual reality (VR) technology have been developed in various forms. This study aimed to investigate the subjective experience of a VR-assisted mental health promotion program for the community population, which was provided in the form of VR experience on a bus to increase accessibility. METHODS: Ninety-six people participated in this study. The relationship between the subjective experience and mental health states such as depression, anxiety, perceived stress, and quality of life was explored. The subjective experience on depression and stress before and after VR program treatment was compared using the Wilcoxon signed-rank test. The satisfaction with the VR-assisted mental health promotion program was examined after using the VR program. RESULTS: The VR-assisted mental health promotion program on a bus significantly improved subjective symptoms such as depression (p=0.036) and perceived stress (p=0.010) among all the participants. Among the high-risk group, this VR program significantly relieved subjective depressive feeling score (p=0.033), and subjective stressful feeling score (p=0.035). In contrast, there were no significant changes in subjective depressive feelings (p=0.182) and subjective stressful feelings (p=0.058) among the healthy group. Seventy-two percent of the participants reported a high level of satisfaction, scoring 80 points or more. CONCLUSION: The findings of this study suggest that the VR-assisted mental health promotion program may effectively improve the subjective depressive and stressful feelings. The use of VR programs on buses to increase of accessibility for the community could be a useful approach for promoting mental health among the population.

The Dropout Rates and Associated Factors in Patients with Mood Disorders in Long-term Naturalistic Treatment.

Objective: Although maintenance treatment for mood disorders is important, the treatment discontinuation rate is reported to be high. This study aimed to investigate the dropout rates and associated factors in mood disorders. Methods: The patients in a mood disorder clinic (n = 535) were examined. Demographic and clinical factors, scores of psychometric scales, time to dropout from initial treatment in patients with bipolar disorder (BP) (n = 288) and depressive disorder (DD) (n = 143) were evaluated based on database of the mood disorder clinic. Results: Among the studied patients with BP and DD, 50% showed dropout in 4.05 and 2.17 years, respectively. The mean survival times were 8.90 years in bipolar disorder I (BP-I), 5.19 years in bipolar II disorder, 3.22 years in bipolar disorder not otherwise specified, 4.24 years in major depressive disorder, and 4.03 years in other depressive disorders. In the multivariate Cox proportional hazards regression model in the BP group, diagnosis BP-I was found to be significantly related to the decrease in dropout rate (hazard ratio [HR] = 0.22, p = 0.001); however, increased past suicide attempt number was significantly related to the increase in dropout rate (HR = 1.13, p = 0.017). In the DD group, none of anxiety disorders as comorbidity, increased scores of openness, and extraversion personality were related to the increase in dropout rate. Conclusion: Patients with BP, especially BP-I, showed a lower dropout rate as compared to patients with other mood disorders.

Infection-related Hospitalizations During Immune Checkpoint Inhibitor Treatment Without Immunosuppressants.

Immunosuppressants are increasingly being used in the clinic to manage immune-related adverse effects. Consequently, the incidence of secondary infections associated with immunosuppression is increasing. However, little is known about primary infections during immune checkpoint inhibitor (ICI) treatment without immunosuppressants. We aimed to evaluate primary infectious diseases during antiprogrammed death ligand-1 immunotherapy without immunosuppressants. We retrospectively screened medical records of 233 patients who underwent ICI treatment for advanced non-small cell lung cancer between January 2014 and May 2018 at National Cancer Center, Republic of Korea. Subsequently, we evaluated the clinical characteristics and treatment outcomes of selected patients hospitalized for potential infectious disease without immunosuppressive treatment (n=80). Eight cases (3.4%) were identified as bacterial pneumonia (n=5) and cellulitis, inflamed epidermoid cyst, and wound infection (n=1 each). The bacterial pathogens Streptococcus pneumoniae and Haemophilus influenzae were identified in 4 patients with pneumonia. The period between the start of ICI treatment and infection varied between 3 and 189 days (median, 24.5 days). Five (62.5%) patients were infected within a month after ICI treatment initiation. All patients were treated with empirical antibiotics and discharged without complications. The median progression-free and overall survival for ICI treatment was 11.5 and 25.5 months, respectively. Six patients experienced ICI-associated adverse effects postinfection: Herpes zoster infection (n=4) and pneumonitis (n=2). Infectious disease independent of immunosuppression is a rare, but possible event in patients with lung cancer receiving ICI treatment. Clinical awareness would enable prompt diagnosis of primary infection during immunotherapy.

Changes of Locomotor Activity by Dopamine D2, D3 Agonist Quinpirole in Mice Using Home-cage Monitoring System.

Objective: : As dopamine is closely linked to locomotor activities, animal studies on locomotor activities using dopaminergic agents were widely done. However, most of animal studies were performed for a short period that there is a lack of longitudinal study on the effects of dopaminergic agents on locomotor activities. This study aimed to examine the longterm effect of a dopamine D2, D3 agonist quinpirole on locomotor activities in mice using a home-cage monitoring system. Methods: : The locomotor activities of Institute Cancer Research mice were measured by infrared motion detectors in home-cages under the 12-hour dark and 12-hour light condition for three days after the quinpirole injection. Quinpirole was injected at a concentration of 0.5 mg/kg intraperitoneally in the beginning of the dark phase. The locomotor activities before and after the quinpirole administration were compared by the Wilcoxon signed-rank test and one-way repeated measures ANOVA. Results: : After the quinpirole administration, the 24-hour total locomotor activity did not change (p = 0.169), but activities were significantly increased in the 12-hour dark phase sum (p = 0.013) and decreased in the 12-hour light phase sum (p = 0.009). Significant increases in the activities were observed in the dark-light difference (p = 0.005) and dark-light ratio (p = 0.005) as well. Conclusion: : This study suggests that quinpirole injection entrains the circadian rest-activity rhythm of locomotor activities. Therefore, quinpirole can be a drug that mediates locomotor activity as a dopamine agonist as well as a modulator of the circadian rhythms.

A Validation Study of Mental Health Monitoring Through a Mobile Application.

OBJECTIVE: Face-to-face evaluation is the most important in psychiatric evaluation, but smart healthcare, including non-face-to-face evaluation, can be beneficial considering the situation in which face-to-face evaluation is limited or the preventive aspect of mental illness. In this paper, we aimed to check whether mental health screening tests have the same significance as paper-based tests even when collected through mobile applications. METHODS: A smart mental healthcare screening test was conducted on the 1,327 community subjects. We measured two indicators of depression (Patient Health Questionnaire 9-item scale, PHQ-9) and anxiety (Generalized Anxiety Disorder 7-item scale, GAD-7) to check mental health conditions. RESULTS: The average Cronbach's alpha value of the PHQ-9 questionnaire was good at 0.870. As a result of PHQ-9's principal component analysis, one component with an eigenvalue of 1 or more was identified, which is suitable to be described as a single factor. The average Cronbach's alpha value of the GAD-7 was 0.919. The structural validity of the GAD-7 was confirmed through principal component analysis. CONCLUSION: Our results show that PHQ-9 and GAD-7 scales performed through mobile applications can have the same meaning as paper-based tests. Surveys using a tablet PC, or smartphone application can monitor residents' mental health and accumulate data. Based on these data, smart mental health management can check the mental health of residents and treat mental illness in connection with medical services.

Cluster Analysis on the Mental Health States in a Community Sample of Young Women During Pre-Pregnancy, Pregnancy, or the Postpartum Period.

OBJECTIVE: It is necessary to identify the mental health types of young women considering the importance of the mental health during the peripartum period. This study aimed to classify the mental health types in a community sample of young women with pre-pregnancy, pregnancy, or the postpartum period. METHODS: A total of 293 young women during pre-pregnancy, pregnancy, or the postpartum period were included in this study. The clinical characteristics of depression, anxiety, perceived stress, and quality of life were assessed. The clinical characteristics of the subject were classified by cluster analysis and compared by analysis of variance. RESULTS: From the cluster analysis, the subjects were classified into three groups. Cluster 1 showed significantly lower depression and anxiety and higher quality of life than those of cluster 2 and 3. Cluster 2 demonstrated significantly higher depression and anxiety and lower quality of life than those of cluster 3 and 1. Cluster 3 represented the intermediate levels between cluster 2 and 1. CONCLUSION: This study suggested that young women during pre-pregnancy, pregnancy, or the postpartum period might be in a good mental health group, a high-risk group requiring active monitoring, or a group in need of treatment. By monitoring mental health, the groups with high risk or requiring treatment could be discovered and proper management for prevention or improvement of mental health and quality of life can be provided.

Influence of Optimism, Social Support, and Spirituality on COVID-19 Stress in Christian Church Community.

OBJECTIVE: Optimism, social support, and spirituality can be important factors related to coronavirus disease-2019 (COVID-19) stress. However, studies investigating the influence and interplay of optimism, social support, and spirituality on COVID-19 simultaneously are still few. This study is aimed to explore the influence of optimism, social support, and spirituality on COVID-19 stress in the Christian church community. METHODS: A total 350 participants were included in this study. This study was cross-sectionally conducted by using an online survey on optimism, social support, spirituality, and COVID-19 stress that were measured by the Life Orientation Test-Revised (LOT-R), Multidimensional Scale of Perceived Social Support Scale (MSPSS), Spiritual Well-Being Scale (SWBS), and COVID-19 Stress Scale for Korean People (CSSK). The prediction models for COVID-19 stress were analyzed by using univariate and multiple linear regression. RESULTS: Based on the results of univariate linear regression, subjective feelings on income (p<0.001) and health status (p<0.001), LOTR (p<0.001), MSPSS (p=0.025), and SWBS (p<0.001) scores were significantly associated with COVID-19 stress. The multiple linear regression model with subjective feelings on income and health status and SWSB score was significant (p<0.001) and explained 17.7% of the variance (R2=0.177). CONCLUSION: This study showed that subjective feeling on low income, those who had poor health status, lower optimism, lower perceived social support, and lower spirituality were significantly affected with COVID-19 stress. Especially, the model with subjective feelings on income and health status, and spirituality showed highly significant effects, despite the interaction with associated factors. To cope with unpredictable stressful situations like the COVID-19 pandemic, integrated interventions on psycho-socio-spiritual aspect are warranted.

Relationship of Circadian Rhythm in Behavioral Characteristics and Lipid Peroxidation of Brain Tissues in Mice.

Objective: This study aimed to explore the relationship among several indices of circadian rhythms and lipid peroxidation of brain tissue in mice. Methods: After entrainment of 4-week-old mice, one group was disrupted their circadian rhythms for three days and the other group for seven days (n = 10, respectively). After a recovery period, the Y-maze test, the elevated plus maze test, the tail suspension test, and the forced swimming test were conducted. To assess lipid peroxidation in brain tissue, thiobarbituric acid reactive substances were measured in the cortex, hippocampus, and cerebellum. Results: When circadian rhythms were disrupted and adapted back to their original rhythm, the recovery time of the 7-day disruption group (median 3.35 days) was significiantly faster than one of the 3-day disruption group (median 4.87 days). In the group with a 7-day disruption, mice that had recovered their rhythms early had higher malondialdehyde levels in their hippocampus compared to those with delayed recovery. The entrainment of circadian rhythms was negatively correlated with the malondialdehyde level of brain tissue. The behavioral test results showed no differences depending on the disruption durations or recovery patterns of circadian rhythms. Conclusion: These results suggest that disruption types, recovery patterns, and the entrainment of circadian rhythms are likely to affect oxidative stress in adolescents or young adult mice. Future study is needed to confirm and specify these results on the effects of circadian rhythms on oxidative stress and age-dependent effects.

Percutaneous Cementoplasty for the Pelvis in Bone Metastasis: 12-Year Experience.

BACKGROUND: In advanced cancer patients, pelvic bone metastasis often causes pain and gait disturbance. The use of percutaneous bone cement [polymethylmethacrylate (PMMA)] injection for pain management and strengthening in pelvic bone metastasis has rarely been reported. To evaluate this method, we aimed to determine surgical outcomes and complications over a long-term follow-up period using a large patient group. PATIENTS AND METHODS: We retrospectively collected data from 178 patients who underwent percutaneous cementoplasty for pelvic metastatic lesions, 201 in total. Surgical outcomes evaluated included pain reduction and improvement of ambulation. Mortality within 1 month after procedure and pulmonary embolism caused by thrombus, fat, tumor emboli, or bone cement were investigated as surgical complications. For long-term survivors, pain relapse and mechanical failure were analyzed. The mean follow-up period was 12.6 months, and there were 159 fatalities at last follow-up. RESULTS: The mean regional pain numerical rating scale scores decreased from 6.1 preoperatively to 2.4 1 month after procedure (p < 0.01). Gait function was maintained, worsened, and uncheckable in 68%, 24%, and 8% of patients, respectively, 1 month after procedure. Of long-term survivors followed up for > 12 months (n = 53), there were no significant changes in serial plain radiographs, and regional pain aggravation was observed in 9%. Pulmonary cement embolism and bone cement implantation syndrome was observed in 11% and 10%, respectively. However, all patients with these complications were asymptomatic. CONCLUSIONS: Percutaneous cement injection into the pelvis is a feasible and safe palliative surgical option for patients with advanced malignancy in terms of pain reduction and maintenance of ambulatory function under regional anesthesia.

Prediction of Locomotor Activity by Infrared Motion Detector on Sleep-wake State in Mice.

OBJECTIVE: Behavioral assessments that effectively predict sleep-wake states were tried in animal research. This study aimed to examine the prediction power of an infrared locomotion detector on the sleep-wake states in ICR (Institute Cancer Research) mice. We also explored the influence of the durations and ways of data processing on the prediction power. METHODS: The locomotor activities of seven male mice in home cages were recorded by infrared detectors. Their sleep-wake states were assessed by video analysis. Using the receiver operating characteristic curve analysis, the cut-off score was determined, then the area under the curve (AUC) values of the infrared motion detector that predicted sleep-wake states were calculated. In order to improve the prediction power, the four ways of data processing on the prediction power were performed by Matlab 2013b. RESULTS: In the initial analysis of raw data, the AUC value was 0.785, but it gradually reached to 0.942 after data summation. The simple data averaging and summation among four different methods showed the maximal AUC value. The 10-minute data summation improved sensitivity (0.889) and specificity (0.901) significantly from the baseline value (sensitivity 0.615; specificity 0.936) (p < 0.001). CONCLUSION: This study suggests that the locomotor activity measured by an infrared motion detector might be useful to predict the sleep-wake states in ICR mice. It also revealed that only simple data summation may improve the predictive power. Using daily locomotor activities measured by an infrared motion detector is expected to facilitate animal research related to sleep-wake states.

Psychometric Properties of Behavioral Checklist for Coping with Stress in Patients with Mood Disorders.

OBJECTIVE: Even though the importance of stress-coping, there is no reliable and valid scale to measure the stress-coping behavior yet. The purpose of this study is to explore the psychometric properties of Behavioral Checklist for Coping with Stress (BCCS). METHODS: A total of 458 subjects including healthy subjects and patients with bipolar or depressive disorders were analyzed. The reliability and validity of BCCS were examined by Chronbach's alpha and exploratory factor analysis using Principal Component Analysis. In order to evaluate criterion-related validity, the Pearson's correlation analyses between factors of BCCS and relevant scales were performed. RESULTS: BCCS showed good Chronobach's alpha (0.695-0.833) and had acceptable validity. Factor 1 and factor 4 of BCCS were negatively correlated with depression, anxiety and positivity correlated with task and problem-solving, avoidance, tension-releasing copings in common. Factor 2 and 3 were positively correlated with impulsivity, emotionality, avoidance, behavioral and verbal aggression and tension-releasing copings in common. Different from factor 2, factor 3 was positively correlated with depression, anxiety and anger-suppression. CONCLUSION: The results of this study suggest that this BCCS might be a reliable and valid scale for measuring stress-coping behaviors. This scale could facilitate research to investigate clinical implications related to behavioral stress-coping.

Anger-Related Characteristics According to Chronotypes in Bipolar or Depressive Disorders.

OBJECTIVE: Though anger was highly associated with eveningness in general population, there is no study on the relationship between chronotype and anger-related characteristics in bipolar or depressive disorders. This study aimed to investigate the difference of anger-related characteristics according to chronotypes in bipolar or depressive disorders. METHODS: Patients with bipolar or depressive disorders (n=238) were included in this study. Their chronotypes and anger-related characteristics were assessed with a self-evaluation of the Composite Scale of Morningness (CSM), the State Trait Anger Expression Inventory (STAXI) and the Anger Coping Scale (ACS). RESULTS: The eveningness group in patients with mood disorders showed the highest scores of anger-trait (p<0.001), anger-expression (p=0.002) and anger-in (p<0.001) in STAXI subscales, verbal aggression (p=0.010) in ACS subscales among three groups, but the morningess group showed the lowest scores of these subscales among three groups. However, there were no significant differences in all subscales of the STAXI and ACS according to diagnostic subtypes in the Friedman test. CONCLUSION: The results of this study suggested that eveningness in patients with mood disorders might be related to anger proneness and maladaptive anger coping. To manage anger emotion in the patients with mood disorders, therapeutic interventions to modulate eveningness might be helpful.

Ceritinib-Induced Organizing Pneumonia in Lung Cancer: A Retrospective Analysis.

BACKGROUND: Ceritinib is a potent selective ALK inhibitor with a manageable safety profile. In anecdotal reports, ceritinib was associated with organizing pneumonia (OP), which could be confused with disease progression. OBJECTIVE: We aimed to delineate the characteristics of OP that occurs during treatment with ceritinib, and evaluate its clinical implications. PATIENTS AND METHODS: We retrospectively analyzed 44 lung cancer patients whose tumors harbored ALK or ROS1 fusions and who had received ceritinib. OP diagnosis was based on radiographic and clinical features. Four OP cases were pathologically confirmed. RESULTS: Among 44 patients, 22 OP events occurred in 16 (36.4%) patients. The median time to the first event was 17.2 weeks (range 6.7-68.7 weeks). All events were grade 1 or 2. Radiographic features were categorized into four patterns: nodular (54.6%), consolidation (27.3%), parenchymal band (4.5%), and ground-glass opacity (GGO) (13.6%). OP improved in 20 events with drug interruption or corticosteroids. The median duration of OP was 11.3 weeks (range 2-24 weeks). Tumor response rate was 75% in OP-positive and 42.9% in OP-negative groups. The median progression-free survival was 16.7 months [95% confidence interval (CI) 10.1-not applicable (NA)] in OP-positive and 5.4 months (95% CI 3.6-8.4) in OP-negative patients (P = 0.004). The median overall survival was 46.2 months (95% CI 38.1-NA) in OP-positive and 10.5 months (95% CI 6.2-18.9) in OP-negative patients (P < 0.001). CONCLUSION: OP occurs frequently during ceritinib treatment and must be distinguished from disease progression. OP could be reversible without fatal complications and its occurrence is associated with better survival outcomes.

Similarities and Differences of Strategies between Bipolar and Depressive Disorders on Stress Coping.

OBJECTIVE: As coping strategies can influence the illness course of mood disorder, they could be potential targets for psychological intervention. The current study investigated the similarities and differences in stress coping styles between bipolar disorder (BD) and depressive disorder (DD). METHODS: Subjects with BD (n=135) and DD (n=100) who met the DSM-IV diagnostic criteria were included in this analysis. Coping strategies were assessed using the coping inventory for stressful situations and depressive symptoms were assessed by Beck depression inventory. RESULTS: The BD group showed significantly more avoidant and task-oriented coping than the DD group (t=2.714, p=0.007; t=2.193, p=0.039). After excluding the effect of the depressive symptoms themselves (by comparing two groups in non-depressive state), the BD group still showed significantly more avoidant and task-oriented coping than the DD group (t=2.040, p=0.045; t=2.556, p=0.013), but when the symptoms of depression get greater, the difference between BD and DD coping strategies were reduced. CONCLUSION: Subjects with BD tend to use more task and avoidant coping than DD subjects. But when the symptoms of depression get greater, the difference in coping strategies between BD and DD were reduced.

Initial M Staging of Rectal Cancer: FDG PET/MRI with a Hepatocyte-specific Contrast Agent versus Contrast-enhanced CT.

BackgroundThe performance of PET/MRI in the determination of distant metastases (M stage) in rectal cancer relative to the current practice with contrast material-enhanced CT is largely unknown.PurposeTo compare the staging of clinical M stage rectal cancer with fluorine 18 fluorodeoxyglucose (FDG) PET/MRI (including dedicated liver and rectal MRI) to that of chest and abdominopelvic CT and dedicated rectal MRI.Materials and MethodsFrom January 2016 to August 2017, patients with newly diagnosed advanced mid to low rectal cancers were recruited for this prospective study (clinicaltrials.gov identifier: NCT0265170). Participants underwent both FDG PET/MRI with dedicated liver and rectal MRI and chest and abdominopelvic CT (the standard-of-care protocol) within 3 weeks of each other. Thereafter, M stage assessment performance was determined by using findings from 6-month clinical follow-up or biopsy as the reference standard. Performance was compared between protocols. Agreement in M stage classification was also assessed. Nonparametric statistical analyses were performed, and P < .05 indicated a significance difference.ResultsSeventy-one participants (28 women; mean age ± standard deviation, 61 years ± 9; age range, 39-79 years) were enrolled. The M stage could not be determined with the standard-of-care protocol in 22 of the 71 participants (31%; 95% confidence interval [CI]: 20.5%, 43.1%) because of indeterminate lesions. However, among these participants, PET/MRI correctly helped identify all 14 (100%; 95% CI: 76.8%, 100%) without metastases and seven of eight (88%; 95% CI: 47.4%, 99.7%) who were later confirmed to have metastases. PET/MRI showed high specificity for ruling out metastatic disease compared with the standard-of-care protocol (98% [54 of 55 participants] vs 72% [40 of 55 participants], respectively; P < .001), without increasing the number of participants with missed metastasis (6% [one of 16 participants] vs 6% [one of 16 participants]; P > .99).ConclusionPET/MRI with dedicated rectal and liver MRI can facilitate the staging work-up of newly diagnosed advanced rectal cancers by helping assess indeterminate lesions, metastases, and incidental findings better than contrast-enhanced CT, obviating for additional imaging work-up.© RSNA, 2019Online supplemental material is available for this article.Clinical trial registration no. NCT02651701.

Accuracy of Model-Based Iterative Reconstruction for CT Volumetry of Part-Solid Nodules and Solid Nodules in Comparison with Filtered Back Projection and Hybrid Iterative Reconstruction at Various Dose Settings: An Anthropomorphic Chest Phantom Study.

OBJECTIVE: To investigate the accuracy of model-based iterative reconstruction (MIR) for volume measurement of part-solid nodules (PSNs) and solid nodules (SNs) in comparison with filtered back projection (FBP) or hybrid iterative reconstruction (HIR) at various radiation dose settings. MATERIALS AND METHODS: CT scanning was performed for eight different diameters of PSNs and SNs placed in the phantom at five radiation dose levels (120 kVp/100 mAs, 120 kVp/50 mAs, 120 kVp/20 mAs, 120 kVp/10 mAs, and 80 kVp/10 mAs). Each CT scan was reconstructed using FBP, HIR, or MIR with three different image definitions (body routine level 1 [IMR-R1], body soft tissue level 1 [IMR-ST1], and sharp plus level 1 [IMR-SP1]; Philips Healthcare). The SN and PSN volumes including each solid/ground-glass opacity portion were measured semi-automatically, after which absolute percentage measurement errors (APEs) of the measured volumes were calculated. Image noise was calculated to assess the image quality. RESULTS: Across all nodules and dose settings, the APEs were significantly lower in MIR than in FBP and HIR (all p < 0.01). The APEs of the smallest inner solid portion of the PSNs (3 mm) and SNs (3 mm) were the lowest when MIR (IMR-R1 and IMR-ST1) was used for reconstruction for all radiation dose settings. (IMR-R1 and IMR-ST1 at 120 kVp/100 mAs, 1.06 ± 1.36 and 8.75 ± 3.96, p < 0.001; at 120 kVp/50 mAs, 1.95 ± 1.56 and 5.61 ± 0.85, p = 0.002; at 120 kVp/20 mAs, 2.88 ± 3.68 and 5.75 ± 1.95, p = 0.001; at 120 kVp/10 mAs, 5.57 ± 6.26 and 6.32 ± 2.91, p = 0.091; at 80 kVp/10 mAs, 5.84 ± 1.96 and 6.90 ± 3.31, p = 0.632). Image noise was significantly lower in MIR than in FBP and HIR for all radiation dose settings (120 kVp/100 mAs, 3.22 ± 0.66; 120 kVp/50 mAs, 4.19 ± 1.37; 120 kVp/20 mAs, 5.49 ± 1.16; 120 kVp/10 mAs, 6.88 ± 1.91; 80 kVp/10 mAs, 12.49 ± 6.14; all p < 0.001). CONCLUSION: MIR was the most accurate algorithm for volume measurements of both PSNs and SNs in comparison with FBP and HIR at low-dose as well as standard-dose settings. Specifically, MIR was effective in the volume measurement of the smallest PSNs and SNs.

Characterization of Tendon-Specific Markers in Various Human Tissues, Tenocytes and Mesenchymal Stem Cells.

Background: Unlike bone, cartilage, or muscle, tendon-specific markers are not well established. The purpose of the study was to investigate expression pattern and level of 6 well-known tendon-specific markers, in various human musculoskeletal tissues, tenocytes, and mesenchymal stem cells (MSCs). Methods: Musculoskeletal tissue samples of tendon, bone, cartilage, nerve, muscle, and fat were obtained from patients undergoing orthopedic surgery. Tenocytes, MSCs from bone marrow, adipose tissue, and umbilical cord were isolated from each tissue and cultured. Six tendon-specific markers, scleraxis (Scx), tenomodulin (TNMD), thrombospondin-4 (TSP-4), tenascin-C (TNC), type I collagen (Col I), and type III collagen (Col III) were investigated in tendon tissue, tenocytes, and MSCs. Results: mRNA levels of 6 tendon-specific markers were significantly higher in tendon tissue that in other connective tissues levels of Scx, TNMD, TSP-4, and Col III immediately decreased after plating tenocytes in culture dishes whereas those of TNC and Col I did not. In comparison with tendon tissue, mRNA levels pattern of Scx, TNMD, and TSP-4 in tenocytes were significantly higher than that in MSCs, but lower than in tendon tissue whereas expression pattern of TNC, Col I and III showed different pattern with each other. Conclusion: This study demonstrated that 6 commonly used tendon-specific markers were mainly expressed in tendon tissue, but that expression level and pattern of the tendon-specific markers with respect to kinds of tissues, culture duration of tenocytes and sources of MSCs.

Effect of miR-155 as a molecular adjuvant of DNA vaccine against VHSV in olive flounder (Paralichthys olivaceus).

Rhabdoviral G protein-based DNA vaccines have been recognized as a useful way to protect cultured fish from rhabdoviral diseases. In Korea, viral hemorrhagic septicemia virus (VHSV) genotype IVa has been the primary culprit of high mortalities of cultured olive flounder (Paralichthys olivaceus). In this study, we inserted a miR-155-expressing cassette into the VHSV's G protein-based DNA vaccine, and analyzed the effects of miR-155 on the antiviral activity and on the vaccine efficacy in olive flounder. Olive flounder fingerlings were intramuscularly (i.m.) immunized with 10 µg/fish (1st experiment) or 1 µg/fish (2nd experiment) of DNA vaccine plasmids. However, there were no significant differences in mortalities and serum neutralization titers between fish immunized with 1 µg and 10 µg plasmids/fish, suggesting that i.m. injection with 1 µg plasmids/fish would be enough to induce effective adaptive immune responses in olive flounder fingerlings. In survival rates, as fish immunized with just G protein expressing plasmids showed no or too low mortalities, the adjuvant effect of miR-155 was not discernible. Also, in the serum neutralization activities, although G gene or G gene plus miR-155 expressing DNA vaccines induced significantly higher activities than control vaccines (PBS and vacant vector), no significant differences were found between G gene alone and G gene plus miR-155 expressing DNA vaccines. In the serum virucidal activity, fish immunized with G gene plus miR-155 expressing DNA vaccine showed significantly higher activity against hirame rhabdovirus (HIRRV) at 3 days post-immunization (d.p.i.) compared to other groups, suggesting that miR-155 produced from the vector can enhance innate immune responses in olive flounder. The significantly enhanced serum virucidal activities against VHSV especially at 28 d.p.i. in the groups immunized with G gene alone and G gene plus miR-155 expressing DNA vaccines reflect the increased antibodies against G protein, which could activate the classical complement pathway and subsequent viral inactivation. As the available information on the DNA vaccines in olive flounder is not sufficient, more diverse researches on the protective efficacy of DNA vaccines are needed to make more practical use of DNA vaccines in olive flounder farms.

Cone-Beam CT Virtual Navigation-Guided Percutaneous Needle Biopsy of Suspicious Pleural Metastasis: A Pilot Study.

Objective: To evaluate the diagnostic performance of cone-beam computed tomography (CBCT) virtual navigation-guided percutaneous pleural biopsy for suspected malignant pleural disease. Materials and Methods: This study enrolled 59 patients (31 males and 28 females; mean age, 63.4 years) with suspected malignant pleural disease diagnosed with CBCT from December 2010 to December 2016. Sixty-three CBCT-guided biopsies were performed using a coaxial system with 18- or 20-gauge cutting needles. Procedural details, diagnostic performance, radiation exposure, and complication rates were investigated. Results: The mean diameter perpendicular to the pleura of 51 focal and 12 diffuse pleural lesions was 1.53 ± 0.76 cm. The mean distance from the skin to the target was 3.40 ± 1.51 cm. Mean numbers of CT acquisitions and biopsies were 3.21 ± 0.57 and 3.05 ± 1.54. Total procedure time and coaxial introducer indwelling time were 11.87 ± 5.59 min and 8.78 ± 4.95 min, respectively. The mean dose area product was 12013.61 ± 7969.59 mGym2. There were 48 malignant, 10 benign, and 5 indeterminate lesions. Sensitivity, specificity, and diagnostic accuracy were 93.8% (45/48), 100% (10/10), and 94.8% (55/58), respectively. Positive and negative predictive values for malignancy were 100% (45/45) and 76.9% (10/13), respectively. Four patients (6.8%) with benign pathology during initial biopsy but still showing a high suspicion of malignancy underwent repeat biopsy and three of them were finally diagnosed with malignant pleural disease. There were three cases of minimal pneumothorax and no grave procedure-related complications. Conclusion: Cone-beam computed tomography-guided biopsy is an accurate and safe diagnostic technique for suspected malignant pleural lesion with reasonable radiation exposure and procedure time.