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The World Health Organization endorses molecular subclassification of endometrial endometrioid carcinomas (EECs). Our objectives were to test the sensitivity of tumor morphology in capturing p53 abnormal (p53abn) cases and to model the impact of p53abn on changes to ESGO/ESTRO/ESP (European Society of Gynaecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology) risk stratification. A total of 292 consecutive endometrial carcinoma resections received at Foothills Medical Centre, Calgary, Canada (2019–2021) were retrieved and assigned to ESGO risk groups with and without p53 status. Three pathologists reviewed the representative H&E‐stained slides, predicted the p53 status, and indicated whether p53 immunohistochemistry (IHC) would be ordered. Population‐based survival for endometrial carcinomas diagnosed during 2008–2016 in Alberta was obtained from the Alberta Cancer Registry. The cohort consisted mostly of grade 1/2 endometrioid carcinomas (EEC1/2; N = 218, 74.6%). One hundred and fifty‐two EEC1/2 (52.1% overall) were stage IA and 147 (50.3%) were low risk by ESGO. The overall prevalence of p53abn and subclonal p53 was 14.5 and 8.3%, respectively. The average sensitivity of predicting p53abn among observers was 83.6%. Observers requested p53 IHC for 39.4% with 98.5% sensitivity to detect p53abn (99.6% negative predictive value). Nuclear features including smudged chromatin, pleomorphism, atypical mitoses, and tumor giant cells accurately predicted p53abn. In 7/292 (2.4%), p53abn upgraded ESGO risk groups (2 to intermediate risk, 5 to high risk). EEC1/2/stage IA patients had an excellent disease‐specific 5‐year survival of 98.5%. Pathologists can select cases for p53 testing with high sensitivity and low risk of false negativity. Molecular characterization of endometrial carcinomas has great potential to refine ESGO risk classification for a small subset but offers little value for approximately half of endometrial carcinomas, namely, EEC1/2/stage IA cases.

Objective The relationship among physical functional decline, low-grade inflammation, and depression remains unclear. The aim of this study was to examine the association between hand grip strength (HGS) and high-sensitivity C-reactive protein (hs-CRP) in a large sample with depression. Methods This study used data obtained from a representative Korean sample of 9,402 people who participated in the seventh Korean National Health and Nutrition Examination Survey. Physical function was assessed using a digital grip strength dynamometer. Depression was identified using a cutoff of 5 on the Patient Health Questionnaire-9 (PHQ-9), and high hs-CPR level was defined as ≥ 3.0 mg/L. Results In older adults (≥ 60 years) with depression, 43.8% of those with high hs-CRP levels had low HGS, compared to 21.8% of those with hs-CRP levels < 3.0 mg/L (p = 0.002). Multivariate analysis revealed that, after adjustments for potentially confounding factors, high hs-CRP was independently associated with lower HGS (B = −2.25; 95% confidence interval = −4.49 to −0.02) in older adults with depression, but not in younger or middle-aged adults with depression. Conclusion These findings suggest a significant correlation between physical functional decline and low-grade inflammation in older adults with depression.

Immunoscore can effectively predict prognosis in patients with colon cancer; however, its clinical application is limited. We modified the Immunoscore and created a tumor immune microenvironment (TIM) classification system for gastric carcinoma. Unlike previous studies that used small sample sizes or focused on particular immune-cell subtypes, our simplified system enables pathologists to classify gastric carcinomas intuitively using H&E-stained sections. Samples from 326 patients with advanced gastric carcinoma were reviewed and analyzed by pathologists using simple determination and digital image analysis. Comprehensive results of cancer-panel sequencing, Epstein-Barr‒virus (EBV) status, and PD-L1, HER2, ATM, PTEN, MET, FGFR2, and EGFR immunohistochemistry were evaluated with respect to the TIM class. The TIM was classified as “hot” (n = 22), “immunosuppressed” (n = 178), “excluded” (n = 83), or “cold” (n = 43). TIM category was significantly associated with numbers of frameshift mutations (P

Background: To improve the rehabilitation team’s awareness of patient mobility and participation by enhancing communication between therapists and nurses and conducting patient education.Methods: This study used a non-equivalent control group with a non-synchronized design. To facilitate communication between therapists and nurses, we used a manual for mobility management to improve the sharing of information on the functional status of patients. We also implemented patient education to improve their awareness of mobility and participation. Finally, we conducted newly devised surveys related to patient functional status and awareness that were applied by therapists and nurses.Results: The nurses reported significantly lower functional levels of patients compared to those assessed by therapists. After the intervention, the kappa values representing the concordance between therapists and nurses improved to almost perfect agreement for transfer ability (κ=0.836), mobility (κ=0.664), and toileting (κ=1.000). We also observed a statistically significant increase in questionnaire scores with respect to nurses’ awareness (p

We aimed to investigate the effect of chronic particulate matter (PM) exposure on bleomycin-induced lung fibrosis in a rat model using chest CT, histopathologic evaluation, and RNA-sequencing. A bleomycin solution was intratracheally administrated to 20 male rats. For chronic PM exposure, after four weeks of bleomycin treatment to induce lung fibrosis, PM suspension (experimental group) or normal saline (control group) was intratracheally administrated for 10 weeks. Chest CT was carried out in all rats, and then both lungs were extracted for histopathologic evaluation. One lobe from three rats in each group underwent RNA sequencing, and one lobe from five rats in each group was evaluated by western blotting. Inflammation and fibrosis scores in both chest CT and pathologic analysis were significantly more aggravated in rats with chronic PM exposure than in the control group. Several genes associated with inflammation and immunity were also upregulated with chronic PM exposure. Our study revealed that chronic PM exposure in a bleomycin-induced lung fibrosis rat model aggravated pulmonary fibrosis and inflammation, proven by chest CT, pathologic analysis, and RNA sequencing.

Objectives: This study demonstrated the positive effect of herbal medication on a suspected idiopathic thrombocytopenic purpura (ITP) patient-a 57-year-old male with suspected ITP and a decreased platelet count.Methods: The patient was treated with an herbal medicine named Nokyongdaebo-tang, and its effect was measured with periodic platelet blood tests.Results: Before taking the herbal medicine, the patient’s blood platelet count was 98 K/μl, but following treatment, the blood platelet count increased to 201 K/μl and maintained a continuously elevated level.Conclusion: The results indicated that herbal medication may improve the blood platelet count of suspected ITP patients.

Despite accumulated evidence on the issue of labor market inequalities on health, the literature to date has failed to consider the changing dynamics of work experiences over a full life course in understanding its association with health. This study takes a holistic approach to understanding labor market trajectories in terms of employment security among wage-earners using a multichannel sequence. Five clusters were found: Secured insider, moderate insiders, vulnerable outsider, precarious workers, and secured labor status but limited income. The findings suggest that labor market inequalities are negatively associated with health outcomes, particularly in the health of the disadvantaged group relative to labor market insiders. Vulnerable outsiders report lower odds of optimal health as well as precarious workers relative to secured insiders. However, the different patterns of association between long-term labor market inequalities and depression were emerged. Future study research could expand to explore the different mechanism of labor market inequalities to self-rated health and depression.

Da-Young Jeong,1 Shin-Hye Kim,1 Moon Young Seo,2 Sin Young Kang,1 Mi Jung Park1 1Department of Pediatrics, Inje University Sanggye Paik Hospital, Seoul, Korea; 2Department of Pediatrics, Uijeongbu Eulji Medical Center, Gyeonggi-do, KoreaCorrespondence: Mi Jung Park; Shin-Hye KimDepartment of Pediatrics, Inje University Sanggye Paik Hospital, 1342, Dongil-ro, Nowon-gu, Seoul, 01757, KoreaTel +82 2 950 8826; +82 2 950 4823Fax +82 2 950 1245; +82 2 950 1246Email pmj@paik.ac.kr; s2635@paik.ac.krPurpose: An adverse lipid profile in adolescence often persists into adulthood, resulting in cardiovascular disease. We aimed to investigate the trends in the prevalence of adverse lipid profiles among Korean adolescents from 2007 to 2018.Patients and Methods: The data were obtained from 9044 adolescents aged 10– 19 years who participated in the Korean National Health and Nutrition Examination Surveys (KNHANES) from 2007 to 2018. Fasting serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) levels were analyzed.Results: Significantly increasing trends in age-standardized prevalence of hypercholesterolemia [from 5.6% to 9.4% in boys (P = 0.004); from 8.1% to 12.4% in girls (P = 0.01)] and hyper-LDL-cholesterolemia [from 4.3% to 8.0% in boys (P = 0.003); from 6.6% to 9.7% in girls (P = 0.035)] were noted in both sexes. In contrast, the prevalence of hypo-HDL-cholesterolemia decreased significantly from 20.0% to 12.5% in boys (< 0.001) and from 12.4% to 6.9% in girls (P < 0.001). There were no significant changes in the prevalence of hypertriglyceridemia and hyper-non-HDL-cholesterolemia in both sexes. Accordingly, the overall prevalence of dyslipidemia showed only a modest decline in boys (from 31.8% to 28.7%) and a stable trend in girls (from 28.9% to 28.2%).Conclusion: The prevalence of hypercholesterolemia and hyper-LDL-cholesterolemia increased and that of hypo-HDL-cholesterolemia decreased among Korean adolescents over the recent 12 years. Further studies are needed to explain these trends and possible associations with lifestyle factors.Keywords: hypercholesterolemia, cholesterol, dyslipidemia, prevalence, KNHANES

Objectives To investigate the occurrence of facet joint ankylosis in the spine of patients with radiographic axial spondyloarthritis (r-axSpA) using low dose computed tomography (ldCT), and to examine the association between facet joint ankylosis and functional impairment. Methods A group of 126 patients with r-axSpA was selected from Incheon Saint Mary's axSpA observational cohort and whole spine ldCT data were examined. Facet joint (right and left, C2–S1) ankylosis was scored from 0–46 (total). The presence of facet joint ankylosis was assessed by two readers, each blinded to the patient data. The inter-reader reliability of facet joint ankylosis scoring was assessed using intraclass correlation coefficients (ICCs). The CT Syndesmophyte Score (CTSS) was assessed. Lumbar spinal mobility was evaluated using the modified Schober test. Functional impairment was measured using the Bath AS functional index (BASFI). Results The ICCs of ankylosed facet joint scores at the cervical, thoracic, lumbar and whole spine were 0.84, 0.88, 0.92 and 0.90, respectively. Facet joint ankylosis was most common in the thoracic spine. Scores for the whole spine correlated positively with the ASDAS, mSASSS and the syndesmophyte score. Multivariate analysis revealed that facet joint ankylosis was significantly associated with decreased lumbar motion. For both readers, the scores for the whole spine were independently associated with BASFI after adjusting for syndesmophyte score and disease activity. Conclusions Facet joint ankylosis in patients with r-axSpA was associated with functional impairment and spinal mobility. Facet joints should be incorporated into a structural damage assessment method.

The implementation of temporal dynamic variables improves the accuracy of spatial accessibility measurements. However, in previous studies, the temporal dynamics were partially incorporated, and a ...

Ovarian clear cell carcinoma (OCCC) and ovarian endometrioid carcinoma (OEC) are both associated with endometriosis but differ in histologic phenotype, biomarker profile, and survival. Our objectives were to refine immunohistochemical (IHC) panels that help distinguish the histotypes and reassess the prevalence of mismatch repair deficiency (MMRd) in immunohistochemically confirmed OCCC. We selected 8 candidate IHC markers to develop first-line and second-line panels in a training set of 344 OCCC/OEC cases. Interobserver reproducibility of histotype diagnosis was assessed in an independent testing cohort of 100 OCC/OEC initially without and subsequently with IHC. The prevalence of MMRd was evaluated using the testing cohort and an expansion set of 844 ovarian carcinomas. The 2 prototypical combinations (OCCC: Napsin A+/HNF1B diffusely+/PR-; OEC: Napsin A-/HNF1B nondiffuse/PR+) occurred in 75% of cases and were 100% specific. A second-line panel (ELAPOR1, AMACR, CDX2) predicted the remaining cases with 83% accuracy. Integration of IHC improved interobserver reproducibility (κ=0.778 vs. 0.882, P

Background: Back pain is associated with a high risk of recurrence. Various physical therapy techniques for back pain have been studied, including reprogramming the central nervous system by integrating sensation and motion with sensory exercise training. Objectives: To aimed verify the effectiveness of sensorimotor training in improving postural stability and pain levels. Design: A randomized controlled trial. Methods: The study population was randomized into a sensory exercise training group and trunk stabilization training group and treated three times a week for 4 weeks. Each group took part in sensorimotor training for 15 minutes or lumbar stabilization exercise for 15 minutes. Results: After the intervention both groups showed Improvements in the variables. There was a significant difference in the dynamic postural stability, limit of stability, and modified visual analog scale scores in the sensorimotor training group compared to the lumbar stabilization exercise group (P

AIMS Genomic inactivation of ARID1B in ARID1A-inactivated tumour and genomic inactivation of SMARCB1 represent two recurrent mechanisms, core SWItch/sucrose non-fermentable (SWI/SNF) complex inactivation, that are associated with de-differentiation in endometrial carcinoma. Approximately one-third of dedifferentiated/undifferentiated endometrial carcinomas (DDEC/UEC) show loss of ARID1B expression with a minor subset showing loss of SMARCB1 expression, but little is known regarding the specificity of ARID1B or SMARCB1 loss in gynaecological tract tumours in general. The aim of this study was to examine the frequency of ARID1B and SMARCB1 loss by immunohistochemistry in a series of gynaecological tract epithelial/mesenchymal neoplasms. METHODS AND RESULTS We evaluated 1849 tumours that included 748 endometrial carcinomas, 101 uterine carcinosarcomas/adenosarcomas, 64 uterine sarcomas, 221 cervical carcinomas and 715 ovarian carcinomas/borderline tumours by tissue microarrays (TMA). We observed ARID1B loss in 35 of 86 (41%) and SMARCB1 loss in three of 86 (3%) DDEC/UEC, but not in any other uterine tumour types examined. ARID1B-deficient DDEC/UEC also showed concurrent loss of ARID1A expression. All SMARCB1-deficient tumours showed loss of MLH1 and PMS2, while 29 of 35 ARID1B-deficient tumours showed loss of MLH1 and PMS2 or loss of MSH6. All ovarian carcinomas/borderline tumours and cervical carcinomas showed intact expression of ARID1B and SMARCB1. CONCLUSION Our findings indicate that the loss of expression of ARID1B or SMARCB1 by immunohistochemistry is highly specific for undifferentiated carcinoma among tumours of the upper gynaecological tract and cervix, and therefore can be used to identify these highly aggressive malignant tumours.

Small extracellular vesicles (sEVs) are nanometer-sized membranous vesicles secreted by cells, with important roles in physiological and pathological processes. Recent research has established the application of sEVs as therapeutic vehicles in various conditions, including heart disease. However, the high risk of off-target effects is a major barrier for their introduction into the clinic. This study evaluated the use of modified sEVs expressing high levels of cardiac-targeting peptide (CTP) for therapeutic small interfering RNA (siRNA) delivery in myocarditis, an inflammatory disease of heart. sEVs were extracted from the cell culture medium of HEK293 cells stably expressing CTP-LAMP2b (referred to as C-sEVs). The cardiac targeting ability of C-sEVs with the highest CTP-LAMP2b expression was >2-fold greater than that of normal sEVs (N-sEVs). An siRNA targeting the receptor for advanced glycation end products (RAGE) (siRAGE) was selected as a therapeutic siRNA and loaded into C-sEVs. The efficiency of cardiac-specific siRNA delivery via C-sEVs was >2-fold higher than that via N-sEVs. Furthermore, siRAGE-loaded C-sEVs attenuated inflammation in both cell culture and an in vivo model of myocarditis. Taken together, C-sEVs may be a useful drug delivery vehicle for the treatment of heart disease., Graphical abstract, Kim et al. sought to further improve cardiac-specific delivery and assess the therapeutic effects of small extracellular vesicles (sEVs) against myocarditis. Our study provides evidence for the efficacy and safety of CTP-expressing sEVs in the treatment of heart disease, exploring their effects in vitro as well as in vivo.

Background Topical calcineurin inhibitors have been used to treat vitiligo, either alone or in combination with phototherapy; however, the long-term safety of these agents remains controversial. Objective To investigate the risk of lymphoma and skin cancer in vitiligo patients who received topical calcineurin inhibitors or phototherapy. Methods A multicenter retrospective cohort study of 25,694 vitiligo patients who received topical calcineurin inhibitors or phototherapy for 6 weeks or more between 2001 and 2019 was performed. Cumulative doses of topical calcineurin inhibitors and total phototherapy sessions were determined. Outcomes were the development of lymphoma or skin cancer after enrollment, confirmed through chart review and pathology reports. Results During 95,203 person-years, 13 cases of lymphoma, 22 of actinic keratosis, 15 of nonmelanoma skin cancer, and 5 of melanoma were observed. The risk of lymphoma and skin cancer was not significantly increased by topical calcineurin inhibitor dose or phototherapy sessions. The interaction between the topical calcineurin inhibitors and phototherapy was not associated with an increased risk of skin cancer. Limitations Retrospective study, individual follow-up duration less than 4 years, and no adjustment for comorbidities and medication history. Not generalizable to other races. Conclusion The long-term risk of skin cancer or lymphoma was not associated with the use of topical calcineurin inhibitors, phototherapy, and both treatments in combination in patients with vitiligo.

The multi‐level feature of GeTe/Sb2Te3 interfacial phase change memory was achieved by applying a designed voltage‐based pulse. It stably demonstrated five multi‐level states without interference for 90 cycles by varying the pulse width. GeTe/Sb2Te3 interfacial phase change memory demonstrated retention time of > 1.0 × 103 s, presenting the significantly low drift coefficient (ν) of

Background/Aims: Current asthma therapies remain unsatisfactory for con trolling airway remodelling in asthma. MicroRNA-21 is a key player in asthma pathogenesis, but the molecular mechanisms underlying its effects on airway remodelling are not completely understood. We investigated the effects of inhibi tion of microRNA-21 on allergic airway inflammation and remodelling. Methods: Female BALB/c mice were divided into four groups: control, ovalbu min-sensitized and -challenged for 3 months, microRNA-negative control-treat ed ovalbumin-treated, and microRNA-21 inhibitor-treated ovalbumin-treated groups. Parameters related to airway remodelling, cytokine production, airway inflammation, and airway hyperresponsiveness were compared between groups. Human bronchial smooth muscle cells were used in a mechanism study. Results: In this asthma model, ovalbumin-sensitized and -challenged mice ex hibited allergic airway inf lammation and airway remodelling. MicroRNA-21 inhibitor-treated mice had fewer inflammatory cells, lower TH2 cytokine produc tion, and suppressed parameters related to remodelling such as goblet cell hyper plasia, collagen deposition, hydroxyproline content, and expression of smooth muscle actin. Inhibition of microRNA-21 decreased transforming growth factor β1 expression and induced Smad7 expression in lung tissue. In human bronchial smooth muscle cells stimulated with transforming growth factor β1, microR NA-21 inhibition upregulated Smad7 expression and decreased markers of airway remodelling. Conclusions: Inhibition of microRNA-21 had both anti-inflammatory and anti-re modelling effects in this model of ovalbumin-induced chronic asthma. Our data suggest that the microRNA-21-transforming growth factor β1-Smad7 axis modu lates the pathogenesis of ovalbumin-induced chronic asthma and in human bron chial smooth muscle cells. MicroRNA-21 inhibitors may be a novel therapeutic target in patients with allergic asthma, especially those with airway remodelling.

Emphysema, a pathological component of chronic obstructive pulmonary disease, causes irreversible damage to the lung. Previous studies have shown that Slit plays essential roles in cell proliferation, angiogenesis, and organ development. In this study, we evaluated the effect of Slit2 on the proliferation and migration of mouse lung epithelial cells and its role in regeneration in an emphysema lung mouse model. Here, we have shown that Slit2/Robo signaling contributes to the regeneration of lungs damaged by emphysema. Mouse epithelial lung cells treated with Slit2 exhibited increased proliferation and migration in vitro. Our results also showed that Slit2 administration improved alveolar regeneration in the emphysema mouse model in vivo. Furthermore, Slit2/Robo signaling increased the phosphorylation of ERK and Akt, which was mediated by Ras activity. These Slit2-mediated cellular signaling processes may be involved in the proliferation and migration of mouse lung epithelial cells and are also associated with the potential mechanism of lung regeneration. Our findings suggest that Slit2 administration may be beneficial for alveolar regeneration in lungs damaged by emphysema., Emphysema: Can lung cells regenerate? A protein called Slit2 may help in treating emphysema by promoting regeneration of cells that line the tiny air sacs called alveoli in the lungs. In the alveoli, oxygen is transferred from the lungs to the blood. In emphysema, the alveoli become damaged, reducing patients’ ability to exhale ‘old’ air and limiting capacity to breathe in fresh, oxygen-rich air. No treatments are available. Yeon-Mok Oh at the University of Ulan College of Medicine, Seoul, South Korea and co-workers investigated whether Slit2, known to be involved in nervous system development, cell proliferation, and migration, could aid in regenerating lung cells. Testing in mouse lung cells produced increased proliferation and migration. Further testing in a mouse model of emphysema showed that the alveoli could regenerate. These results hold promise for developing new treatments for emphysema.

PURPOSE This study was performed to evaluate the usefulness of lymphoscintigraphy in predicting the surgical outcomes of lymphaticovenous anastomosis (LVA) in a patient with extremity lymphedema. PATIENTS AND METHODS We retrospectively evaluated 133 patients with extremity lymphedema who underwent lymphoscintigraphy followed by LVA surgery from February 2018 to March 2020. Lymphoscintigraphic findings were evaluated on the following parameters: the extent of dermal backflow (small/large), lymphatic flow patterns (trunk flow pattern/proximal-restricted pattern/distal-restricted pattern), visualization of lymph nodes, and collateral lymphatic vessels. The mean circumferential difference change before and after surgery, circumferential reduction (CR) rate (%), was used as the clinical outcome variables. RESULTS A decrease in circumference was observed in 93 (69.9%) of 133 patients after LVA. The extent of dermal backflow and lymphatic flow patterns was significantly correlated with improved clinical outcomes after LVA. The large extent of the dermal backflow group showed a more significant CR rate than the small extent (19.27% vs 1.24%, P = 0.005). The TP group showed the most significantly decreased CR rate to 21.46%, and the proximal-restricted pattern and distal-restricted pattern groups were -2.49% and -5.33%, respectively (P < 0.001). Multivariate analysis revealed that dermal backflow and lymphatic flow patterns were independent predictors of therapeutic outcome (P < 0.001). CONCLUSIONS Our study demonstrates that pretreatment lymphoscintigraphy may help predict the therapeutic effect of LVA in patients with extremity lymphedema. Furthermore, dermal backflow and lymphatic flow patterns are independent predictors of CR rate after LVA surgery for extremity lymphedema.

The city of Pohang in South Korea experienced substantial damage following the ML 5.4 earthquake on 15 November 2017. Damage surveys immediately after the earthquake revealed significant spatial variations in damage intensity across the epicentral area. We collected ambient noise data (three‐component seismic data) from 124 locations in Pohang, covering a total area of 17 km × 20 km, and applied the horizontal‐to‐vertical spectral ratio technique to estimate the resonance frequency, amplification factor and vulnerability of the ground to seismic shaking. Spatial variations exhibited by these three parameters are strongly correlated and consistent with variations in local geology. By comparing the distribution of the ground vulnerability index (Kg) with the damage distribution (or intensity) documented by the Korea Meteorological Administration following the earthquake, we confirm that the site effect is the prevailing effect that influences damage intensity in this region. We also demonstrate that Kg is an efficient proxy for identifying relatively fragile zones during ground shaking: in areas with a reported damage intensity of VIII, the proportion of the area with Kg > 20 is as high as 78.2%. Given that the study area has experienced a recent moderate earthquake, with significant economic consequences, our new results and analytical techniques will provide valuable information for future urbanization projects.

Introduction The expansion of smoke-free policies has reduced the prevalence of second-hand smoke (SHS) exposure; however, declines differ according to socioeconomic positions. We evaluated the trends in socioeconomic inequalities related to SHS exposure in nonsmoking Korean adults from 2008 to 2018. Methods We analyzed 30,027 nonsmoking adults from the Korea National Health and Nutrition Examination Survey 2008 to 2018. We evaluated trends in urine cotinine levels, self-reported prevalence of SHS exposure at workplaces and homes, and people exhibiting nonmeasurable urine cotinine levels between 2008 and 2018. To evaluate the yearly decline differences of urine cotinine levels according to socioeconomic positions, we calculated the interaction effects of year and education, household incomes, and occupation from linear regression analysis. Results In the last 11 years, the geometric means of urine cotinine levels decreased from 3.53 (95% CI 2.96–4.19) ng/mL to 0.60 (0.57–0.64) ng/mL in males, and from 2.36 (2.03–2.73) ng/mL to 0.53 (0.51–0.56) ng/mL in females. The prevalence of SHS exposure at workplaces and homes also declined. In the multivariate model, the interaction effects between education and years were significant; therefore, indicating a substantial yearly decline of urine cotinine levels in higher educated individuals. The interaction effects between household incomes and years were only significant among males; the interaction effects between occupations and years were not significant. Conclusions SHS exposure in nonsmoking Korean adults has consistently decreased; however, socioeconomic inequalities related to SHS exposure by education level have widened. Policies targeting socioeconomically disadvantaged populations should be implemented to decrease the disparities of SHS exposure. Implications Along with tobacco control policies, the prevalence of self-reported and urinary cotinine verified SHS exposure has decreased in the last 11 years. In contrast, the socioeconomic inequalities related to SHS exposure by education level have increased over time. This study emphasizes the need for implementing tobacco control policies to reduce disparities of SHS exposure.

Purpose This study investigated radioactive iodine treatment (RAIT) patterns and the secondary cancer incidence among children and young adults receiving RAIT after thyroidectomy for thyroid cancer. Methods This population-based cohort study used the Health Insurance Review and Assessment database of South Korea to identify a total of 18 617 children and young adults (0–29 years) who underwent thyroidectomy for thyroid cancer between 2008 and 2018. We recorded age at surgery, sex, the interval from surgery to RAIT, the doses of RAI, the number of RAIT sessions, and secondary cancer incidence. Results A total of 9548 (51.3%) children and young adults underwent 1 or more RAIT sessions. The initial dose of RAIT was 4.35 ± 2.19 GBq. The overall RAIT frequency fell from 60.9% to 38.5%, and the frequency of high-dose RAIT (>3.7 GBq) fell from 64.2% to 36.5% during the observational period. A total of 124 cases of secondary cancer developed during 120 474 person-years of follow-up; 43 (0.5%) in the surgery cohort and 81 (0.8%) in the RAIT cohort. Thus, the RAIT cohort was at an increased risk of secondary cancer (adjusted hazard ratio 1.52 [95% confidence interval 1.03–2.24], P = 0.035). Conclusion The proportion of children and young adults receiving RAIT, and the RAI dose, fell significantly over the observational period. RAIT was associated with secondary cancers. This is of major concern in the context of child and young adult thyroid cancer survivors.

OBJECTIVE High blood pressure (BP) increases the risk of dementia; however, few studies have reported on the risk of dementia in patients with low-risk, early-grade hypertension. We investigated the protective effect of controlled BP on risk of dementia in treated, low-risk, grade 1 hypertensive patients from the entire National Health Insurance Service National Health Examinee cohort. METHODS We selected grade 1 hypertension (140-159/90-99 mmHg) patients with low risk, diagnosed in 2005-2006. All patients (N = 128 665) were classified into controlled (average BP

Ipsilateral hemiparesis is a rare and challenging sign in clinical neurological practice. Although the etiology of this manifestation is poorly understood, recent studies have attempted to probe the pathomechanism of this sign with advanced radiological techniques. Additional knowledge about the lesion and unraveling the pathomechanisms causing neurological impairments are important to predict the prognosis and clinical course and to aid in rehabilitation. Therefore, we present a case of a patient with a traumatic subdural hematoma on the left hemisphere and left spastic hemiparesis. Using diffusion tensor imaging (DTI), we concluded that the right corticospinal tract injury caused by compression of the cerebral peduncle accounted for the ipsilateral hemiparesis, also known as Kernohan's notch phenomenon. Thus, this case report highlights the usefulness of the newer radiological techniques, such as DTI, to identify the pathomechanisms of neurological presentations.

Objective Hepatitis B surface antigen (HBsAg) is known as the hallmark of hepatitis B virus (HBV) infection. This study aimed to determine whether an HBsAg neutralization test is necessary to accurately interpret HBsAg test results. Methods Initially reactive HBsAg specimens from a 5-year period, with cutoff index values between 1.0 and 2.0, were subjected to neutralization confirmatory testing using an Elecsys HBsAg Confirmatory test kit (Roche Diagnostics GmbH. Mannheim, Germany). Results The neutralization test showed 46.1% positive (confirmed positive group) and 53.9% negative (confirmed negative group) results from the total specimens. Among the confirmed negative group, 79.5% of patients were confirmed to be negative for the current infection, whereas 4 patients in the chronic hepatitis B subgroup showed a neutralization percentage close to 40%. More than half of patients in the confirmed positive group were considered to be in the hepatitis B e antigen-negative inactive HBsAg carrier phase. Conclusion In populations with intermediate HBV prevalence, a neutralization test is necessary to confirm an HBsAg result and reduce the false positive and false negative rates of initial HBsAg tests.

Purpose Virtual gifts have emerged as a common feature of online communities, social gaming and social networks. This paper aims to examine how network-related variables and gift-seeding impact virtual gift sales. The network variables include gift-giver centrality and gift-giving dispersion, capturing, respectively, the relative importance of gift-givers in a network and their tendency to give gifts to a greater or lesser number of network peers. Gift-seeding tactics capture social network firms’ attempts to stimulate virtual gift purchases by awarding virtual gifts to network members. Design/methodology/approach This study develops and estimates a fixed-effects panel data regression model to analyze virtual gift purchase data for a large social network service. Findings Gift-giver centrality, gift-giving dispersion and gift-seeding increase virtual gift purchases. Increases in consumers’ receipt of seed gifts from social network firms (“direct seeding”) and from other consumers (“indirect seeding”) increases virtual gift purchases. However, the extent to which consumers give seed gifts to their friends in the social network (“seed mediation”) does not affect sales. Greater gift-giver centrality amplifies (attenuates) the positive effects of direct (indirect) seeding. At greater levels of gift-giving dispersion, the effects of indirect seeding and seed mediation become negative. Furthermore, gift-seeding has spillover effects on virtual good (non-gift) purchases. Research limitations/implications This study’s data, drawn from a South Korean social network service, offer unique and valuable social network information on actual virtual gift purchases and their seeding. Future research should replicate the results of the study outside the South Korean context. Practical implications Given the effects reported in this study, social network firms can facilitate the purchases of virtual gifts by improving the targeting of consumers in social networks and gift-seeding tactics. Originality/value This study uniquely examines the individual and interactive effects of network-related variables and gift-seeding on virtual gift sales. The study is seminal in its examination of how gift-seeding can be used as a marketing tactic to increase virtual gift purchases.

Objectives To assess the efficacy of an endothelin receptor antagonist (ERA) and phosphodiesterase type5 inhibitors (PDE5is) for treating SSc-related digital ulcers (DUs). Methods This prospective, multicentre, observational cohort study recruited patients with active SSc-related DUs from 13 medical centres in South Korea. The primary outcome was time to cardinal ulcer (CU) healing. A secondary outcome was time to new DU occurrence. Patients were followed up 4, 8, 12 and 24 weeks after treatment initiation. Results Sixty-three patients were analysed. Their mean age was 49.9 years (s.d. 11.4) and 49 were female. Twenty-eight had limited SSc. Forty-nine patients received ERA, 11 received a PDE5i (9 sildenafil, 1 udenafil and 1 tadalafil) and 3 received other medication. The hazard ratio (HR) for time to CU healing in the ERA group vs the PDE5i group was 0.75 (95% CI 0.35, 1.64; P = 0.47) in an unadjusted model and 0.80 (95% CI 0.36, 1.78; P = 0.59) in a model adjusted for age, sex, use of calcium channel blockers (CCBs), total DU number and initial CU area. The HR for new DU development in the ERA group vs the PDE5i group was 0.39 (95% CI 0.16, 0.93; P = 0.03) in an unadjusted model and 0.32 (95% CI 0.13, 0.81; P = 0.02) in an adjusted model. No patients receiving CCBs developed new DUs at 24 weeks. Conclusion Time to CU healing is comparable for ERA and PDE5i. ERAs are more effective in reducing new DU occurrence than PDE5is. CCBs may be effective as a background medication.

BACKGROUND PfFAD3 transgenic soybean expressing omega‐3 fatty acid desaturase 3 of Physaria produces increased level of α‐linolenic acid in seed. Composition data of non‐transgenic conventional varieties is important in the safety assessment of the genetically‐modified (GM) crops in the context of the natural variation. RESULTS The natural variation was characterized in seed composition of 13 Korean soybean varieties grown in three locations in South Korea for 2 years. Univariate analysis of combined data showed significant differences by variety and cultivation environment for proximates, minerals, anti‐nutrients, and fatty acids. Percent variability analysis demonstrated that genotype, environment and the interaction of environment with genotype contributed to soybean seed compositions. Principal component analysis and orthogonal projections to latent structure discriminant analysis indicated that significant variance in compositions was attributable to location and cultivation year. The composition of three PfFAD3 soybean lines for proximates, minerals, anti‐nutrients, and fatty acids was compared to a non‐transgenic commercial comparator (Kwangankong, KA), and three non‐transgenic commercial varieties grown at two sites in South Korea. Only linoleic and linolenic acids significantly differed in PfFAD3‐1 lines compared to KA, which were expected changes by the introduction of the PfFAD3‐1 trait in KA. CONCLUSION Genotype, environment, and the interaction of environment with genotype contributed to compositional variability in soybean. PfFAD3‐1 soybean is equivalent to the conventional varieties with respect to these components. © 2020 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

TP53 mutations are implicated in the progression of mucinous borderline tumors (MBOT) to mucinous ovarian carcinomas (MOC). Optimized immunohistochemistry (IHC) for TP53 has been established as a proxy for the TP53 mutation status in other ovarian tumor types. We aimed to confirm the ability of TP53 IHC to predict TP53 mutation status in ovarian mucinous tumors and to evaluate the association of TP53 mutation status with survival among patients with MBOT and MOC. Tumor tissue from an initial cohort of 113 women with MBOT/MOC was stained with optimized IHC for TP53 using tissue microarrays (75.2%) or full sections (24.8%) and interpreted using established criteria as normal or abnormal (overexpression, complete absence, or cytoplasmic). Cases were considered concordant if abnormal IHC staining predicted deleterious TP53 mutations. Discordant tissue microarray cases were re-evaluated on full sections and interpretational criteria were refined. The initial cohort was expanded to a total of 165 MBOT and 424 MOC for the examination of the association of survival with TP53 mutation status, assessed either by TP53 IHC and/or sequencing. Initially, 82/113 (72.6%) cases were concordant using the established criteria. Refined criteria for overexpression to account for intratumoral heterogeneity and terminal differentiation improved concordance to 93.8% (106/113). In the expanded cohort, 19.4% (32/165) of MBOT showed evidence for TP53 mutation and this was associated with a higher risk of recurrence, disease-specific death, and all-cause mortality (overall survival: HR = 4.6, 95% CI 1.5-14.3, p = 0.0087). Within MOC, 61.1% (259/424) harbored a TP53 mutation, but this was not associated with survival (overall survival, p = 0.77). TP53 IHC is an accurate proxy for TP53 mutation status with refined interpretation criteria accounting for intratumoral heterogeneity and terminal differentiation in ovarian mucinous tumors. TP53 mutation status is an important biomarker to identify MBOT with a higher risk of mortality.

Although metabolic intratumoral heterogeneity (ITH) gives important value on treatment responses and prognoses, its association with treatment outcomes have not been reported in gastric cancer (GC). We aimed to evaluate temporal changes in metabolic ITH and the associations with treatment responses, progression-free survival (PFS), and overall survival (OS) in advanced GC patients. Eighty-five patients with unresectable, locally advanced, or metastatic GC were prospectively enrolled before the first-line palliative chemotherapy and underwent [18F]FDG PET at baseline (TP1) and the first response follow-up evaluation (TP2). Standardized uptake values (SUVs), volumetric parameters, and textural features were evaluated in primary gastric tumor at TP1 and TP2. Of 85 patients, 44 had partial response, 33 had stable disease, and 8 progressed. From TP1 to TP2, metabolic ITH was significantly reduced (P P max at TP2, a high kurtosis at TP2 and larger decreases in the coefficient of variance were associated with better PFS. A low SUVmax at TP2, larger decreases in the metabolic tumor volume and larger decreased in the energy were associated with better OS. Age older than 60 years and responders also showed better OS. An early reduction in metabolic ITH is useful to predict treatment outcomes in advanced GC patients.

Although hepatotoxicity induced by immune checkpoint inhibitors (ICPIs) can cause severe clinical complications, the risk factors associated with hepatotoxicity have rarely been investigated. The purpose of this study was to determine the potential risk factors for the incidence of hepatotoxicity and for time to ICPI-induced hepatotoxicity. Patients who received ICPIs (atezolizumab, nivolumab, pembrolizumab, and ipilimumab) were included in this retrospective 2-center study. Collected data included sex, age, body weight, body surface area, Eastern Cooperative Oncology Group performance status, underlying disease, liver metastasis, programmed cell death ligand-1 expression, interval from previous chemotherapy, and concomitant drug use. Among the 194 patients, patients who experienced hepatotoxicity after ICPI administration was 64.4% (n=125) in all grade and 10.8% (n=21) in grade III or higher. Multivariate analysis showed that patients aged 30-50 and 50-70 years had increased risks of hepatotoxicity by 4.9-fold (95% confidence interval, 1.3-18.0) and 2.7-fold (95% confidence interval, 1.3-5.5), respectively, compared with those older than 70 years. The use of acetaminophen increased the occurrence of hepatotoxicity by 2.1 times; the attributable risk was 53.2%. Male patients and patients younger than 65 years had around 1.5-fold increased hazard of time to reach hepatotoxicity. Patients treated with 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors had a 4.7-fold higher risk of grade III-IV hepatotoxicity compared with those without HMG-CoA reductase inhibitors; the attributable risk was 78.8%. In conclusion, close monitoring of liver function is recommended, especially in male patients, patients younger than 65 years old, and when there is concomitant use of hepatotoxic drugs including acetaminophen and HMG-CoA reductase inhibitors.

The use of biomarkers to guide patient and therapy selection has gained much attention to increase the scope and complexity of targeted therapy options and immunotherapy. Clinical trials provide a basis for discovery of biomarkers, which can then aid in development of new drugs. To that end, samples from cancer patients, including DNA, RNA, protein, and the metabolome isolated from cancer tissues and blood or urine, are analyzed in various ways to identify relevant biomarkers. In conjunction with nucleotide-based, high-throughput, next-generation sequencing techniques, therapy-guided biomarker assays relying on protein-based immunohistochemistry play a pivotal role in cancer care. In this review, we discuss the current knowledge regarding DNA and protein biomarkers for cancer immunotherapy.

More digital retailers are expanding into offline channels by launching products in partners' stores, despite the mature offline shopping. Despite this extensive phenomenon, little attention is focused on the impact of offline product launches on sales. This paper examines how offline product launches via third-party offline stores affects online and mobile purchases, and extends understanding by investigating the moderating effect of offline store intensity. We analyze data obtained from a digital-first beauty retailer through a difference-in-differences analysis using a bivariate negative binomial distribution model. Empirical results show offline product launches are synergistic with online and mobile purchases, especially with respect to the latter. In addition, offline store intensity weakens the positive effect of offline product launches on online purchases, whereas it does not moderate the effect on mobile purchases. Moreover, we provide insights into developing geo-targeting launch strategies through what-if analyses. Our findings provide critical managerial implications for digital retailing.

BACKGROUND AND OBJECTIVES Ambient particulate matter (PM) in real urban air pollution (RUA) is an environmental health risk factor associated with increased cardiac events. This study investigated the threshold level to induce arrhythmia, as well as arrhythmogenic mechanism of RUA that mainly consisted of PM

In the United States, 8 out of 10 elders, 65 or older, have at least one chronic disease. Their care likely falls mostly to family members; many experience financial strain associated with providin...

Purpose MicroRNA-21 (miR-21) influences the Th2 immune pathway by suppressing the expressions of interleukin (IL)-12 and interferon (IFN)-γ. The effects of miR-21 suppression on alveolar macrophage polarization and airway inflammation are not known. Methods BALB/c and miR-21 knockout (KO) mice were sensitized and challenged with ovalbumin (OVA). The anti-miR-21 antagomir was administered to BALB/c mice by intranasal inhalation from the day of OVA sensitization. Changes in cell counts, cytokine levels in bronchoalveolar lavage fluid (BALF), and airway hyperresponsiveness (AHR) were examined. Total, M1, and M2 macrophages were examined in the lung tissues by immunohistochemistry (IHC). M2 macrophages from the OVA mice lung were inhaled into the anti-miR-21 antagomir-treated asthmatic mice. Moreover, the polarization of M0 to M2 macrophages upon IL-4 stimulation was analyzed after anti-miR-21 antagomir transfection. Results The miR-21 KO mice showed decreases in AHR, total cell and eosinophil counts in BALF, and in the levels of IL-4, IL-5, IL-10, and IL-13. Expression of IL-12 and IFN-γ were increased in the miR-21 KO mice. Peribronchial inflammation and goblet cell dysplasia were significantly decreased in the lung tissues of miR-21 KO OVA mice compared to the wild type OVA mice. IHC for M1, M2, and total macrophage in the lung tissues showed that miR-21 inhalation suppressed alveolar M2 macrophages in KO mice. M2 macrophage inhalation restored AHR and eosinophilic airway inflammation in the miR-21 antagomir-treated mice. Moreover, anti-miR-21 antagomir transfection decreased the expression of M2 markers and increased the expression of M1 markers in M0 macrophages after IL-4 stimulation. Conclusions The results suggest that miR-21 antagonism could suppress alveolar M2 macrophage polarization, decreasing not only the Th2 eosinophilic airway inflammation but also AHR and airway remodeling process.