Drug Persistence and Incidence of Active Tuberculosis of Tumor Necrosis Factor Alpha Inhibitors Versus Tocilizumab as the First-Line Biological Treatment in Patients with Rheumatoid Arthritis: A Nationwide Population-Based Retrospective Cohort Analysis.

INTRODUCTION: Drug persistence may be a surrogate marker that reflects both long-term efficacy and safety in clinical settings, and tuberculosis (TB) is considered as one of the most important opportunistic infections after the biological treatment in rheumatoid arthritis (RA). We aimed to compare drug persistence and incidence of TB between tumor necrosis factor alpha (TNFα) inhibitors and tocilizumab in patients with RA using data from the Korean Health Insurance Review and Assessment Service database. METHODS: In this analysis, 5449 patients with RA who started TNFα inhibitors, such as adalimumab, etanercept, infliximab, and golimumab or tocilizumab, as the first-line biological therapy between January 2014 and December 2017 were analyzed and followed up until December 2019. Drug persistence was defined as the duration from initiation to first discontinuation, and TB was defined as the prescription of > 2 anti-TB medications after the initiation of biologics. RESULTS: TNFα inhibitors and tocilizumab were prescribed in 4202 (adalimumab, 1413; etanercept, 1100; infliximab, 769; golimumab 920) and 1247 patients with RA, respectively. During the analysis period, 2090 (49.7%) and 477 (38.3%) patients with RA discontinued TNFα inhibitors and tocilizumab, respectively, and 42 patients with RA developed TB (TNFα inhibitors, 33; tocilizumab, 9). After adjustment for confounding factors, TNFα inhibitors were significantly associated with a higher risk of discontinuation compared with tocilizumab (hazard ratio (HR) 1.63, p < 0.001). In subgroup analysis, all types of TNFα inhibitors, except for infliximab, demonstrated a significantly lower persistence rate compared with tocilizumab. There was no significant difference in TB incidence between tocilizumab and TNFα inhibitors. In subgroup analysis, infliximab has a significantly higher risk of TB compared with tocilizumab (HR 2.84, p = 0.02). CONCLUSION: In this analysis, tocilizumab had longer persistence than TNFα inhibitors with a similar incidence of TB. Our analysis has limitations: (1) The HIRA database lacks clinical details like disease activity and joint damage extent, potentially influencing the analysis results. (2) Reasons for discontinuing biological agents were not available. (3) TB diagnoses may be inaccurate because of missing microbiological results. (4) We did not analyze the impact of treating latent TB infection on TB development post-biological treatment, despite mandatory screening in Korea.

Ginkgo biloba extract ameliorates skin fibrosis in a bleomycin-induced mouse model of systemic sclerosis.

Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by skin and internal organ fibrosis and obliterative vasculopathy. Few effective treatments are currently available for fibrosis in SSc, therefore, demand persists for novel therapies. Although use of Ginkgo biloba extract (GBE) has been reported to improve blood circulation and alleviate liver and lung fibrosis, its effect on skin fibrosis in SSc remains unclear. In this study, the effects and underlying mechanisms of GBE on skin fibrosis in bleomycin (BLM)-induced mouse model of SSc was investigated. GBE significantly reduced dermal thickness and protein levels of profibrotic factors in the BLM-induced SSc mouse model. Moreover, GBE inhibited the gene expression of profibrotic factors, such as COL1A1, α-SMA, and connective tissue growth factor (CTGF), in fibroblasts by suppressing transforming growth factor (TGF)-ß signaling. Furthermore, GBE inhibited the transdifferentiation of adipocytes into myofibroblasts. Thus, our findings suggest that GBE is a promising therapeutic candidate for the treatment of SSc.

PRMT5 mediates FoxO1 methylation and subcellular localization to regulate lipophagy in myogenic progenitors.

Development is regulated by various factors, including protein methylation status. While PRMT5 is well known for its roles in oncogenesis by mediating symmetric di-methylation of arginine, its role in normal development remains elusive. Using Myod1Cre to drive Prmt5 knockout in embryonic myoblasts (Prmt5MKO), we dissected the role of PRMT5 in myogenesis. The Prmt5MKO mice are born normally but exhibit progressive muscle atrophy and premature death. Prmt5MKO inhibits proliferation and promotes premature differentiation of embryonic myoblasts, reducing the number and regenerative function of satellite cells in postnatal mice. Mechanistically, PRMT5 methylates and destabilizes FoxO1. Prmt5MKO increases the total FoxO1 level and promotes its cytoplasmic accumulation, leading to activation of autophagy and depletion of lipid droplets (LDs). Systemic inhibition of autophagy in Prmt5MKO mice restores LDs in myoblasts and moderately improves muscle regeneration. Together, PRMT5 is essential for muscle development and regeneration at least partially through mediating FoxO1 methylation and LD turnover.

Analysis of appropriate duration of colchicine prophylaxis to maximize the persistence of xanthine oxidase inhibitors as the first-line urate-lowering therapy in patients with gout using the Korean Health Insurance Review and Assessment Service database.

INTRODUCTION: We investigated the appropriate duration of colchicine prophylaxis to maximize the persistence of xanthine oxidase inhibitors (XOIs) as first-line urate-lowering therapy (ULT) in patients with gout. This was a nationwide population-based retrospective cohort study using the Korean Health Insurance Review and Assessment database. METHODS: Patients with gout aged ≥20 years who were newly initiated on XOIs, such as allopurinol or febuxostat, from July 2015 to June 2017 and received these medications for ≥6 months were analyzed and followed up until June 2019. Persistence of XOIs was compared according to the 6-month duration of colchicine prophylaxis. For additional subgroup analysis, we also compared the persistence of XOIs according to the 3-month duration of colchicine prophylaxis. RESULTS: This study included 43 926 patients. The frequencies of patients with gout receiving colchicine prophylaxis for ≥6 months and ≥3 months were 6.3% and 7.6%, respectively. Allopurinol (65.2%) was prescribed more frequently than febuxostat (34.8%). During the study period, 23 475 patients (53.4%) stopped using XOIs. Colchicine prophylaxis for ≥6 months did not significantly reduce the risk of XOI discontinuation in multivariable Cox regression models. Colchicine prophylaxis for ≥3 months was significantly associated with a lower risk of non-persistence to XOIs after adjusting for confounding factors (hazard ratio = 0.95, p = .041). CONCLUSION: Our data suggest that at least 3 months of colchicine prophylaxis may be more appropriate than at least 6 months in terms of maximizing the persistence of XOIs in patients with gout.

Erratum: Correction of Author's Affiliation in the Article "Changing Patterns of Medical Visits and Factors Associated With No-show in Patients With Rheumatoid Arthritis During COVID-19 Pandemic".

This corrects the article on p. e423 in vol. 35, PMID: 33316859.

High Baseline Neutrophil-to-Lymphocyte Ratio Could Serve as a Biomarker for Tumor Necrosis Factor-Alpha Blockers and Their Discontinuation in Patients with Ankylosing Spondylitis.

BACKGROUND: This study explores the association of neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR), and platelet-to-lymphocyte (PLR) ratios with the 3-month treatment response and persistence of tumor necrosis factor-alpha (TNF-α) blockers in patients with ankylosing spondylitis (AS). METHODS: This retrospective cohort study investigated 279 AS patients who were newly initiated on TNF-α blockers between April 2004 and October 2019 and 171 sex- and age-matched healthy controls. Response to TNF-α blockers was defined as a reduction in the Bath AS Disease Activity Index of ≥50% or 20 mm, and persistence referred to the time interval from the initiation to discontinuation of TNF-α blockers. RESULTS: Patients with AS had significantly increased NLR, MLR, and PLR ratios as compared to controls. The frequency of non-response at 3 months was 3.7%, and TNF-α blockers' discontinuation occurred in 113 (40.5%) patients during the follow-up period. A high baseline NLR but not high baseline MLR and PLR showed an independently significant association with a higher risk of non-response at 3 months (OR = 12.3, p = 0.025) and non-persistence with TNF-α blockers (HR = 1.66, p = 0.01). CONCLUSIONS: NLR may be a potential marker for predicting the clinical response and persistence of TNF-α blockers in AS patients.

Diagnostic Value of Neutrophil-to-Lymphocyte, Platelet-to-Lymphocyte, and Monocyte-to-Lymphocyte Ratios for the Assessment of Rheumatoid Arthritis in Patients with Undifferentiated Inflammatory Arthritis.

Background: To investigate the diagnostic performance of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) in the diagnosis of rheumatoid arthritis (RA) in subjects with undifferentiated inflammatory arthritis (UIA). Methods: This retrospective cohort study investigated 201 female patients with UIA (≥1 swollen joint) and 280 age-matched, healthy female controls. "Clinical RA" was defined based on the clinical judgment of a rheumatologist and "disease-modifying anti-rheumatic drugs (DMARDs) RA" was defined as a case of initiating DMARDs treatment within 6 months after the first visit. "Classified RA" was defined as fulfilling the 2010 classification criteria for RA. Receiver operating characteristics were used to determine the optimal cut-off value. Results: UIA patients had a significantly higher NLR, PLR, and MLR than the controls. Among the 201 UIA patients, 65 (32.3%), 63 (31.3%), and 61 (30.3%) subjects were classified as clinical RA, DMARDs RA, and classified RA, respectively. At a cut-off of 0.24, MLR showed moderate accuracy for the diagnosis of DMARDs RA (sensitivity, 65.1%; specificity, 62.3%; area under the curve [AUC], 0.701; p < 0.001). However, the diagnostic accuracies of NLR and PLR were low. Conclusions: MLR may be used as a complementary diagnostic indicator for RA diagnosis in patients with UIA.

Associations of Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio and Monocyte-to-Lymphocyte Ratio with Osteoporosis and Incident Vertebral Fracture in Postmenopausal Women with Rheumatoid Arthritis: A Single-Center Retrospective Cohort Study.

Background and Objectives: We investigated whether nutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphoycte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) are associated with the presence of osteoporosis (OP) and vertebral fractures in patients with rheumatoid arthritis (RA). Materials and Methods: This retrospective cohort study included 413 postmenopausal patients with RA and 200 healthy controls who underwent dual-energy X-ray absorptiometry (DEXA) between January 2005 and December 2017. DEXA examination data were defined as the index date, and all laboratory values were measured within one month from the index date. OP was defined as a T-score < −2.5, and incident vertebral fractures were defined as the first occurrence of non-traumatic fractures after the index date. NLR, PLR, and MLR measures were dichotomized by a median split (low vs. high). Results: The median NLR, PLR, and MLR in RA patients were significantly higher than those in controls. The frequencies of OP of the lumbar spine, hip, and either site in postmenopausal patients with RA were 24.7%, 15.5%, and 32%, respectively, and were significantly higher than those in controls. After adjusting for confounding factors, a high baseline NLR was significantly associated with OP at either site (OR = 1.61, p = 0.041). In addition, high baseline NLR (OR = 2.11, p = 0.025) and PLR (OR = 2.3, p = 0.011) were related with the presence OP at hip. During the follow-up period, 53 (12.8%) patients with RA developed vertebral fractures incidentally. In multivariable Cox regression models, a high baseline NLR (HR = 4.72, p < 0.001), PLR (HR = 1.96, p = 0.024), and MLR (HR = 2.64, p = 0.002) were independently associated with a higher risk of incidental vertebral fractures. Conclusions: Our data suggest that NLR, PLR, and MLR can be used as potential markers of systemic bone loss among individuals with RA.

Status of Glucocorticoid-Induced Osteoporosis Preventive Care in Korea: A Retrospective Cohort Study on the Korean National Health Insurance Service Database.

Background and Objectives: It is crucial to prevent osteoporosis in patients receiving long-term glucocorticoid (GC) treatment. This study aimed to investigate the frequency and associated factors of preventive care for glucocorticoid-induced osteoporosis (GIOP) in Korea. Materials and Methods: Using the Korean National Health Insurance Service database, we identified 37,133 individuals aged ≥ 20 years who commenced long-term (≥90 days) oral GC between 2011 and 2012. High-quality GIOP preventive care was defined as either a bone mineral density (BMD) test, calcium and/or vitamin D supplementation, or prescription osteoporosis medications within 6 months of GC initiation. Multivariable logistic regression models were used to calculate odds ratios (ORs) for associated factors for high-quality GIOP preventive care. Results: The mean age was 49.8 years, and 18,476 (49.8%) patients were female. The frequency of high-quality GIOP preventive care was only 3.68% (BMD test, 1.46%; osteoporosis medications, 1.65%; calcium/vitamin D, 1.63%). Increasing age (OR = 2.53, p < 0.001; 40-49 years, OR = 3.99, p < 0.001; 50-59 years, OR = 5.17, p < 0.001; 60-69 years, OR = 8.07, p < 0.001; ≥70 years, respectively), systemic autoimmune disease (OR = 3.08, p < 0.001), rural residence (OR = 1.19, p = 0.046), concomitant hyperthyroidism (OR = 1.58, p = 0.007), and malignancy (OR = 1.59, p < 0.001) were significantly associated with a higher likelihood of receiving high-quality GIOP preventive care. Male sex (OR = 0.26, p < 0.001) and GC prescription in primary care clinics and nursing hospitals (OR = 0.66, p < 0.001) were associated with a lower rate of high-quality GIOP preventive care. Conclusions: Most Korean patients treated with GC did not receive appropriate preventive care for GIOP in real-world practice. More efforts are needed by clinicians to prevent, screen, and treat GIOP.

Resting State Brain Network Function in Elderly: The Formation of Social Ties.

BACKGROUND: The purpose of this study is to determine the relevance of the relationship between brain network and the social ties management. METHODS: Participants are based on 52 Korean seniors aged 65 and older who live in Ganghwa-gun, Incheon. We used a closed-triad index (CTI), which is the most basic unit of analysis in the study of group phenomena. This index is a social networking variable that has been shown to have a different implication depending on the subject's condition and role. After two questionnaire surveys were conducted at three years intervals, participants were classified into an increased group and a decreased group according to the change of CTI. Resting-state fMRI analysis were followed to investigate the difference of brain networks between groups. RESULTS: According to the analysis of the study, the whole participants who had increased in number of CTI has higher local efficiency than the group of the participants who had no effect or decreased in CTI. CONCLUSIONS: Our study suggests that social relationship, which is substantially related to brain network, is a major factor in successful aging. Lastly, since there is a restriction that the study cannot explain the causal aspect of the brain network and the triad-relationship, there is a need for further investigation.

ANTECEDENTES: El propósito de este estudio fue determinar la relevancia de la relación entre la red cerebral y el manejo de los lazos sociales. MÉTODO: los participantes son 52 adultos mayores coreanos de 65 años o más que viven en Ganghwa-gun, Incheon. Utilizamos un índice de tríada cerrada (CTI), que es la unidad de análisis más básica en el estudio de los fenómenos grupales. Este índice es una variable de red social que ha demostrado tener una implicación diferente dependiendo de la condición y el rol del sujeto. Después de realizar dos encuestas por cuestionario a intervalos de tres años, los participantes se clasificaron en un grupo aumentado y un grupo disminuido de acuerdo con el cambio de CTI. Se siguió el análisis de fMRI en estado de reposo para investigar la diferencia de las redes cerebrales entre los grupos. RESULTADOS: Según el análisis del estudio, todos los participantes que habían aumentado en número de CTI tienen una mayor eficiencia local que el grupo de participantes que no tuvieron ningún efecto o disminuyeron en CTI. CONCLUSIONES: Nuestro estudio sugiere que la relación social que está sustancialmente relacionada con la red cerebral es un factor importante en el envejecimiento exitoso. Por último, dado que existe una restricción de que el estudio no puede explicar el aspecto causal de la red cerebral y la relación tríada, existe la necesidad de una mayor investigación.

Changing Patterns of Medical Visits and Factors Associated with No-show in Patients with Rheumatoid Arthritis during COVID-19 Pandemic.

BACKGROUND: The main barrier to the effective rheumatoid arthritis (RA) therapy is poor adherence. Coronavirus disease 2019 (COVID-19) pandemic have led to a significant change in the pattern and the number of medical visits. We assessed changing patterns of medical visits and no-show, and identified factors associated with no-show in patients with RA during COVID-19 pandemic. METHODS: RA patients treated with disease-modifying antirheumatic drugs at least 6 months who had been in remission or those with mild disease activity were observed for 6 months from February to July 2020. No-show was defined as a missed appointment that was not previously cancelled by the patient and several variables that might affect no-show were examined. RESULTS: A total of 376 patients and 1,189 appointments were evaluated. Among 376 patients, 164 patients (43.6%) missed appointment more than one time and no-show rate was 17.2% during COVID-19 pandemic. During the observation, face-to-face visits gradually increased and no-show gradually decreased. The logistic regression analysis identified previous history of no-show (adjusted odds ratio [OR], 2.225; 95% confidence interval [CI], 1.422-3.479; P < 0.001) and fewer numbers of comorbidities (adjusted OR, 0.749; 95% CI, 0.584-0.961; P = 0.023) as the independent factors associated with no-show. CONCLUSION: Monthly analysis showed that the no-show rate and the pattern of medical visits gradually changed in patients with RA during COVID-19 pandemic. Moreover, we found that previous history of no-show and fewer numbers of comorbidities as the independent factors associated with no-show.

Association of Regional Bone Synthetic Activities of Vertebral Corners and Vertebral Bodies Quantified Using 18F-Fluoride Positron Emission Tomography with Bone Mineral Density on Dual Energy X-ray Absorptiometry in Patients with Ankylosing Spondylitis.

We investigated whether the bone-synthetic activities of vertebral bodies or vertebral corners quantified using 18F-fluoride positron emission tomography (PET) was associated with bone mineral density (BMD) at the corresponding lumbar vertebrae in ankylosing spondylitis (AS) at each vertebra level. We analyzed 48 lumbar vertebrae in 12 AS patients who underwent 18F-fluoride PET and dual energy X-ray absorptiometry (DXA). The mean standardized uptake values (SUVmean) of the vertebral body and corners from L1 to L4 were measured using the spatially separated region of interest (ROI). The L1-L4 BMDs were calculated based on the DXA ("conventional BMD"). The BMD of the internal vertebral bodies was measured by manually drawing ROIs to represent the trabecular BMD ("alternative BMD"). After adjusting the within-patient correlation, the 18F-fluoride SUVmean of the vertebral corners but not that of vertebral bodies was significantly related with the conventional BMD of the vertebra. Otherwise, the 18F-fluoride uptake of both the vertebral and vertebral bodies was significantly related with the alternative BMD. The bone-synthetic activities of the vertebral corners may be more closely related with BMD than those of the vertebral bodies, suggesting that the effects of regional bone metabolism at the vertebral corners and bodies on BMD differ in AS.

Higher serum uric acid levels are associated with reduced risk of hip osteoporosis in postmenopausal women with rheumatoid arthritis.

Although the positive correlation between serum uric acid (UA) levels and bone mineral density (BMD) has been reported in the general population, there are little data regarding the effect of serum UA levels on bone loss in patients with rheumatoid arthritis (RA).We investigated whether increased serum UA levels were associated with a reduced risk of osteoporosis in postmenopausal women with RA.In this retrospective cross-sectional study, 447 postmenopausal female patients with RA and 200 age-matched, postmenopausal healthy controls underwent BMD examination by dual energy x-ray absorptiometry and serum UA levels measurement. Osteoporosis was diagnosed when the T-score was <-2.5.The median UA level in postmenopausal RA patients was found to be significantly lower than that in the healthy women (4 vs 4.1 mg/dL, P = .012) and the frequency of osteoporosis incidence in the lumbar spine, hip, and either site in RA patients was 25.5%, 15.9%, and 32.5%, respectively; the values were significantly higher than those of the controls. After adjusting for confounding factors, a significantly lower risk for osteoporosis of the hip in RA patients was observed within the highest quartile (odds ratio [OR] = 0.37, 95% confidence interval [CI] = 0.16-0.72, P = .021) and the second highest quartile (OR = 0.44, 95% CI = 0.2-0.95, P = .038) of serum UA levels as compared with the lowest quartile, but this association was not found to be consistent with respect to the lumbar spine. Serum UA levels also showed an independently positive correlation with femoral neck BMD (ß = 0.0104, P = .01) and total hip BMD (ß = 0.0102, P = .017), but not with lumbar BMD.Our data suggest that UA may exert a protective effect on bone loss in RA, especially in the hip.

Platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio as potential makers for digital ulcers and interstitial lung disease in patients with systemic sclerosis: cross-sectional analysis of data from a prospective cohort study.

In this study, we aimed to investigate the association of platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) with clinical manifestations in patients with systemic sclerosis (SSc). We conducted a cross-sectional analysis of data collected from a cohort study of 114 female patients with SSc and of 304 age-matched, healthy, female controls recruited from a tertiary rheumatology center. Patients with digital ulcers (DU) included those with either active or healed ulcers. Interstitial lung disease (ILD) was diagnosed on detection of diffuse ground-glass opacity or pulmonary fibrosis on chest X-ray or on high-resolution computed tomography. Patients with SSc had significantly higher PLR and NLR than ealthy controls. Of 114 patients with SSc, 35 (30.7%) and 54 (47.4%) patients had DU (active: 12, healed: 23) and ILD, respectively. PLR and NLR in SSc patients with concurrent DU or ILD were significantly higher than that in those without these respective complications. The PLR (OR = 1.008, 95% CI 1.002-1.015), but not the NLR, was independently associated with the presence of DU in SSc patients, based on multivariable logistic regression models. Additionally, both PLR (OR = 1.008, 95% CI 1.001-1.014) and NLR (OR = 1.515, 95% CI 1.066-2.155) correlated independently with the presence of ILD. However, both the PLR and NLR showed no significant association with the modified Rodnan skin score, pulmonary arterial hypertension, and gastrointestinal involvement. Our results suggest that PLR and NLR could be considered as potential biomarkers of DU and ILD, in patients with SSc.

Comparison of persistence rates between allopurinol and febuxostat as first-line urate-lowering therapy in patients with gout: an 8-year retrospective cohort study.

INTRODUCTION/OBJECTIVES: Lifelong urate-lowering therapy (ULT) with xanthine oxidase inhibitors (XOIs), such as allopurinol and febuxostat, is the cornerstone of gout treatment. This study aimed to compare drug persistence between allopurinol and febuxostat as first-line ULT in patients with gout in real practice. METHOD: In this retrospective cohort study, we evaluated 602 patients with gout in whom allopurinol or febuxostat was newly initiated from December 2011 to November 2018 at a tertiary rheumatology centre. Persistence was defined as the duration from the first description date to the end of treatment with XOIs or the end of the study period (November 2019). RESULTS: Among the 602 gout patients, the mean age was 60.2 years and 234 (38.9%) patients had tophi. Allopurinol and febuxostat were started in 237 (39.3%) and 365 (60.6%) patients, respectively. During the study period, 282 (46.8%) patients stopped taking XOIs, and the most common reason for XOI withdrawal was poor health literacy (61.3%). The 1- and 5-year persistence rates of XOIs were 67.2% and 40.9%, respectively. In the Kaplan-Meier analysis, persistence rates of allopurinol were significantly lower than those of febuxostat (p < 0.001). In the multivariable Cox regression model, allopurinol use was a significant risk factor for discontinuation of XOIs (HR = 2.01, p < 0.001). In addition, the presence of tophi and symptom duration < 24 months was independently associated with a higher risk of XOI withdrawal. CONCLUSIONS: Long-term persistence of XOIs was suboptimal, and allopurinol had worse persistence rates than febuxostat among patients with gout. Key Points • Long-term persistence of xanthine oxidase inhibitors (XOIs) as first-line urate-lowering therapy (ULT) among patients with gout was suboptimal, and the major reason for XOI discontinuation was poor health literacy in our study. • We demonstrated that allopurinol had worse persistence rates than febuxostat among patients with gout, suggesting that febuxostat is a better option for long-term ULT in light of medication adherence in a real-world setting. • Patients with gout with tophi and shorter symptom duration were found to be at high risk for poor persistence of XOIs.

Impact of Immobilization on Interfractional Errors for Upper Extremity Soft Tissue Sarcoma Radiation Therapy.

INTRODUCTION/BACKGROUND: Owing to the rare nature and presentation of upper extremity soft tissue sarcomas (STSs) and the high mobility of associated anatomy, various patient positioning strategies are used for radiation therapy. The purpose of this study is to measure the interfractional setup errors associated with upper extremity sarcomas using different immobilization methods through cone-beam computed tomography (CBCT) images. METHODS: All patients treated with daily CBCT guidance for upper extremity STSs during 2014-2015 were identified and triaged based on type of immobilization. After defining an optimal region of interest for image registration, daily CBCT images were automatically registered to reference CT images to quantify positional discrepancies. Means and standard deviations were calculated, and one-way analysis of variance was calculated to determine significance of data. RESULTS: Seventeen patients with upper extremity sarcoma met inclusion criteria: 13 were treated to the shoulder/axilla/upper arm and 4 to the arm/elbow/forearm. Three main types of immobilization were identified: vacuum cradle with custom thermoplastic shell, vacuum cradle alone, and no immobilization accessory used. Patient repositioning occurred if translational and rotational displacements were larger than 1 mm and 5°, respectively, as per institutional guidelines. Patient repositioning rates were 18% for vacuum cradle with thermoplastic shells, 15% for vacuum cradles only, and 6% for no immobilization accessories. Mean translational displacements in right/left (R/L), superior/inferior (S/I), and anterior/posterior (A/P) directions were -0.04 ± 0.33 cm, 0.32 ± 0.33 cm, and 0.12 ± 0.25 cm for vacuum cradle with thermoplastic shell; 0.25 ± 0.10 cm, -0.07 ± 0.22 cm, and 0.00 ± 0.17 cm for vacuum cradle alone; and 0.14 ± 0.15 cm, 0.08 ± 0.45 cm, and -0.01 ± 0.24 cm for no immobilization. For all patients, rotational displacements in the pitch, roll, and yaw were 0.15 ± 1.99°, 0.31 ± 2.11°, and -0.21 ± 1.76°, respectively. There were significant (P < .05) differences in systematic error values for all translational and rotational axes between immobilization methods. CONCLUSION: Large interfractional errors, especially in the rotational axes, were observed, regardless of immobilization strategy. Small study population and unequal representation of different parts of the upper extremity are identified limitations. The need for better immobilization techniques for upper extremity STS treatments is clearly demonstrated.

Pore Parameters-Dependent Adsorption Behavior of Volatile Organic Compounds on Graphene-Based Material.

Mesoporous graphenes (MPGs) with interpenetrating porous networks are successfully obtained by the pyrolysis of composite gel consisting of graphite oxide (GO) and the amphiphilic triblock copolymer (Pluronic P123) under Ar atmosphere, wherein P123 is used as a soft-template. The as-prepared composite gel is obtained following self-assembly and freeze-drying. The obtained MPGs have high BET specific surface area (531-746 m2 g-1 and ink-bottle like pores with three dimensional interconnected network. Furthermore, the specific surface area and porous parameters such as pore volume, pore size, and pore size distribution of MPGs can be rationally controlled by regulating the initial mass ratio of P123 to GO. With the increase of P123 ratio, the average mesopore size is decreased from ∼16.4 nm to ∼9.5 nm, which is similar to the diameter size of P123 micelles. Also, the adsorption capacities of MPG-20 for 52 indoor air standard components (100 µg mL-1, Supelco) are compared with two different materials, namely commercial porous polymers (2,6-diphenyleneoxide) and reduced graphene oxide (RGO). The result shows that MPG-20 has significantly better adsorption capacity than RGO but also similar or slightly better than commercial porous polymer. The mesoporous structure and surface chemistry of MPGs were the most important factors for the enhancement of the adsorption efficiency for volatile organic compounds.

Development of Latent Fingermarks on Nonporous and Semiporous Substrates Using Photoluminescent Eu(Phen)2 Complex Intercalated Clay Hybrids with Enhanced Adhesion.

In forensic science, developing latent fingermarks using powders is a critical, general method to identify individuals. Photoluminescent Eu(Phen)2 complex intercalated clay hybrids have been used to improve the visualization of fingermarks on nonporous (glass and polymer film) and semiporous (euro and dollar banknotes) substrates. An ion exchange reaction has been successfully used to intercalate Eu(Phen)2 complex ions into the interlayer spacing of two different Na+ -clays, Na+ -montmorillonite and Na+ -hectorite, with different primary particle sizes. To change the surface properties of the obtained hybrid to be more lipophilic, the hydroxyl groups at the edge of the hectorite hybrid were modified with hexadecyltrimethoxysilane via silylation. We investigated the correlation of the size and surface properties of the hybrids with their adhesion to fingermark residues. Fingermarks were successfully visualized using hybrids under UV illumination. In particular, ridge details on semiporous substrates can be more clearly seen using hybrids with smaller primary particles and greater lipophilicity.

Biosynthetic substitution of tyrosine in green fluorescent protein with its surrogate fluorotyrosine in Escherichia coli.

Introduction of a fluorine moiety into green fluorescent protein offers an interesting novel spectral variant. The calculated binding energy of fluorotyrosine (F-Tyr) (-8.42 kcal/mol) for tyrosyl tRNA synthetase was moderately higher than that of tyrosine (Tyr) (-8.36 kcal/mol). This result directly correlated with the expression level of F-Tyr containing GFP (38 mg/l), which was comparably higher than that of the parent GFP expression level (34 mg/l). Finally, we generated a model structure for GFP to assess possible interaction in the chromophore of the protein structure, which plays an important role in determining the spectral and folding behaviors of the F-Tyr incorporated GFP variant.

Bi-layer gravure printed nanoscale thick organic layers for organic light emitting diode.

The gravure printed single layer structure and bi-layer structure of MEH-PPV/rubrene organic light emitting diodes (OLEDs) were investigated in this work. Typically, the formation of bi-layers in polymer light emitting diodes (PLEDs) is challenging. The brightness and efficiency polymer light emitting materials were enhanced by the gravure printed bi-layer structure in this work. The layer structure of the OLED devices was glass/ITO/PEDOT:PSS/active layer/LiF/Al. The active layers were made using two different processes-one was a gravure printed single organic layer made of a blended mixture of MEH-PPV and rubrene, and the other was a gravure printed bi-layer of MEH-PPV and rubrene. The gravure printed bi-layer devices exhibited a higher brightness and efficiency than the blended devices. The efficiency of the bi-layer MEH-PPV/rubrene structure was improved by a factor of 1.6 approximately 3.2, and the brightness was improved by a factor of 1.9 approximately 2.0 compared to the blended single layer structure. This work demonstrated that organic bi-layers could be formed using gravure printing technology and the bi-layer structure exhibited a higher efficiency than the blended single layer structure.