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BACKGROUND:Plasminogen activator inhibitor-1 (PAI-1) is induced in airways by virus and may mediate asthmatic airway remodeling. We sought to evaluate if genetic variants and early life lower respiratory infections jointly affect asthma risk. METHODS:We included Latino children, adolescents, and young adults aged 8-21 years (1736 subjects with physician-diagnosed asthma and 1747 healthy controls) from five U.S. centers and Puerto Rico after excluding subjects with incomplete clinical or genetic data. We evaluated the independent and joint effects of a PAI-1 gain of function polymorphism and bronchiolitis / Respiratory Syncytial Virus (RSV) or other lower respiratory infections (LRI) within the first 2 years of life on asthma risk, asthma exacerbations and lung function. RESULTS:RSV infection (OR 9.9, 95%CI 4.9-20.2) and other LRI (OR 9.1, 95%CI 7.2-11.5) were independently associated with asthma, but PAI-1 genotype was not. There were joint effects on asthma risk for both genotype-RSV (OR 17.7, 95% CI 6.3-50.2) and genotype-LRI (OR 11.7, 95% CI 8.8-16.4). A joint effect of genotype-RSV resulted in a 3.1-fold increased risk for recurrent asthma hospitalizations. In genotype-respiratory infection joint effect analysis, FEV1% predicted and FEV1/FVC % predicted were further reduced in the genotype-LRI group (β -2.1, 95% CI -4.0 to -0.2; β -2.0, 95% CI -3.1 to -0.8 respectively). Similarly, lower FEV1% predicted was noted in genotype-RSV group (β -3.1, 95% CI -6.1 to -0.2) with a trend for lower FEV1/FVC % predicted. CONCLUSIONS:A genetic variant of PAI-1 together with early life LRI such as RSV bronchiolitis is associated with an increased risk of asthma, morbidity, and reduced lung function in this Latino population.

Innate and adaptive immune responses change with increasing age and affect the course of diseases. Previous study investigated immunologic alteration in Western nasal polyps (NP) which is mostly eosinophilic. However, there are no reports regarding age-related immune changes of non-eosinophilic NP (NE-NP) which is a predominant subtype in Asian population.A total of 153 subjects, including 20 with control, 63 with chronic rhinosinusitis (CRS) without NP (CRSsNP), and 70 with CRS with NP were enrolled. Age-related changes in computed tomography (CT), cytokines and clinical information were investigated. Tissue samples were analyzed for protein levels of IL-5, IL-17A, IL-23, interferon (IFN)-γ, CCL-11, and CXCL-8, using Luminex immunoassay and for mRNA expression levels of interleukin (IL)-5, IL-17A, IL-23p19, IFN-γ, CCL-11, CXCL-1, CXCL-2, CXCL-8, and CXCR2 by quantitative RT-PCR. Immunohistochemistry (IHC) was performed for the number of inflammatory cells.We observed that Lund-Mackay CT scores decreased with age in NE-NP. The number of human neutrophil elastase-positive cells and myeloperoxidase gene expression decreased in older patients with NE-NP, but not in control subjects, CRSsNP, and E-NP. Neutrophil-associated cytokines including IL-17A and IL-23, were negatively correlated with age in NE-NP at the protein and mRNA levels. Additionally, the expression of CXCR2, a receptor for CXCL-1 and CXCL-2, was decreased with age in NE-NP. However, there were no age-related changes in blood neutrophil count, and neutrophil-recruiting chemokines such as CXCL-1, CXCL-2, and CXCL-8. Elderly NE-NP patients showed better endoscopic scores at 12 months after surgery compared with the non-elderly.Age-related decline in neutrophil inflammation may favorably affect postoperative results in elderly patients with NE-NP.

Non-eosinophilic nasal polyps (NPs) show less inflammatory changes and are less commonly associated with lower airway inflammatory disorders such as asthma, compared with eosinophilic NPs. However, the development of non-eosinophilic NPs which is a predominant subtype in Asian population still remains unclear.A total of 81 patients (45 with non-eosinophilic NPs and 36 with eosinophilic NPs) were enrolled. Clinical information and computed tomography (CT), endoscopic, and histological findings were investigated. Tissue samples were analyzed for total IgE levels and for mRNA expression levels of interleukin (IL)-4, IL-5, IL-13, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-17A, IL-22, IL-23p19, transforming growth factor (TGF)-β1, TGF-β2, TGF-β3, and periostin. Immunostaining assessment of Ki-67 as a proliferation marker was performed.We found that epithelial in-growing patterns such as pseudocysts were more frequently observed in histological and endoscopic evaluations of non-eosinophilic NPs, which was linked to increase epithelial staining of Ki-67, a proliferating marker. Eosinophilic NPs were characterized by high infiltration of inflammatory cells, compared with non-eosinophilic NPs. To investigate the developmental course of each subtype, CT was analyzed according to CT scores and subtypes. Non-eosinophilic NPs showed more localized pattern and maxillary sinus involvement, but lesser olfactory involvement in early stage whereas eosinophilic NPs were characterized by diffuse ethmoidal and olfactory involvement. In addition, high ethmoidal/maxillary (E/M) CT scores, indicating ethmoidal dominant involvement, were one of surrogate markers for eosinophilic NP. E/M CT scores was positively correlated with levels of TH2 inflammatory markers, including IL-4, IL-5, periostin mRNA expression and total IgE levels in NPs, whereas levels of the TH1 cytokine, IFN- γ were inversely correlated. Moreover, if the combinatorial algorithm meet the three of the four markers, including IL-5 (0.316), and E/M ratio (

The rumen microbial ecosystem is a complex system where rumen fermentation processes involve interactions among microorganisms. There are important relationships between diet and the ruminal bacterial composition. Thus, we investigated the ruminal fermentation characteristics and compared ruminal bacterial communities using tag amplicon pyrosequencing analysis in Yanbian yellow steers, which were fed linseed oil (LO) and propionate precursors. We used eight ruminally cannulated Yanbian yellow steers (510 ± 5.8 kg) in a replicated 4 × 4 Latin square design with four dietary treatments. Steers were fed a basal diet that comprised 80% concentrate and 20% rice straw (DM basis, CON). The CON diet was supplemented with LO at 4%. The LO diet was also supplemented with 2% dl-malate or 2% fumarate as ruminal precursors of propionate. Dietary supplementation with LO and propionate precursors increased ruminal pH, total volatile fatty acid concentrations, and the molar proportion of propionate. The most abundant bacterial operational taxonomic units in the rumen were related to dietary treatments. Bacteroidetes dominated the ruminal bacterial community and the genus Prevotella was highly represented when steers were fed LO plus propionate precursors. However, with the CON and LO diet plus malate or fumarate, Firmicutes was the most abundant phylum and the genus Ruminococcus was predominant. In summary, supplementing the diets of ruminants with a moderate level of LO plus propionate precursors modified the ruminal fermentation pattern. The most positive responses to LO and propionate precursors supplementation were in the phyla Bacteriodetes and Firmicutes, and in the genus Ruminococcus and Prevotella. Thus, diets containing LO plus malate or fumarate have significant effects on the composition of the rumen microbial community.

BackgroundPlasminogen activator inhibitor-1 (PAI-1) is induced in airways by virus and may mediate asthmatic airway remodeling. We sought to evaluate if genetic variants and early life lower respiratory infections jointly affect asthma risk.MethodsWe included Latino children, adolescents, and young adults aged 8-21 years (1736 subjects with physician-diagnosed asthma and 1747 healthy controls) from five U.S. centers and Puerto Rico after excluding subjects with incomplete clinical or genetic data. We evaluated the independent and joint effects of a PAI-1 gain of function polymorphism and bronchiolitis / Respiratory Syncytial Virus (RSV) or other lower respiratory infections (LRI) within the first 2 years of life on asthma risk, asthma exacerbations and lung function.ResultsRSV infection (OR 9.9, 95%CI 4.9-20.2) and other LRI (OR 9.1, 95%CI 7.2-11.5) were independently associated with asthma, but PAI-1 genotype was not. There were joint effects on asthma risk for both genotype-RSV (OR 17.7, 95% CI 6.3-50.2) and genotype-LRI (OR 11.7, 95% CI 8.8-16.4). A joint effect of genotype-RSV resulted in a 3.1-fold increased risk for recurrent asthma hospitalizations. In genotype-respiratory infection joint effect analysis, FEV1% predicted and FEV1/FVC % predicted were further reduced in the genotype-LRI group (β -2.1, 95% CI -4.0 to -0.2; β -2.0, 95% CI -3.1 to -0.8 respectively). Similarly, lower FEV1% predicted was noted in genotype-RSV group (β -3.1, 95% CI -6.1 to -0.2) with a trend for lower FEV1/FVC % predicted.ConclusionsA genetic variant of PAI-1 together with early life LRI such as RSV bronchiolitis is associated with an increased risk of asthma, morbidity, and reduced lung function in this Latino population.

Inhibiting the functional role of negative regulators in immune cells is an effective approach for developing immunotherapies. The serine/threonine kinase hematopoietic progenitor kinase 1 (HPK1) involved in the T-cell receptor signaling pathway attenuates T-cell activation by inducing the degradation of SLP-76 through its phosphorylation at Ser-376, reducing the immune response. Interestingly, several studies have shown that the genetic ablation or pharmacological inhibition of HPK1 kinase activity improves the immune response to cancers by enhancing T-cell activation and cytokine production; therefore, HPK1 could be a promising druggable target for T-cell-based cancer immunotherapy. To increase the immune response against cancer cells, we designed and synthesized KHK-6 and evaluated its cellular activity to inhibit HPK1 and enhance T-cell activation. KHK-6 inhibited HPK1 kinase activity with an IC50 value of 20 nM and CD3/CD28-induced phosphorylation of SLP-76 at Ser-376 Moreover, KHK-6 significantly enhanced CD3/CD28-induced production of cytokines; proportion of CD4+ and CD8+ T cells that expressed CD69, CD25, and HLA-DR markers; and T-cell-mediated killing activity of SKOV3 and A549 cells. In conclusion, KHK-6 is a novel ATP-competitive HPK1 inhibitor that blocks the phosphorylation of HPK1 downstream of SLP-76, enhancing the functional activation of T cells. In summary, our study showed the usefulness of KHK-6 in the drug discovery for the HPK1-inhibiting immunotherapy.

With the concept of "healthy lifestyle" deeply rooted in people's minds, the sports service industry is thriving, which has resulted in intense competition. The sports service industry must improve its service quality to be competitive. Customer orientation is the key factor for enterprises to gain competitive advantage. With the in-depth understanding of internal marketing in the service industry. Managers have realized that treating employees as internal consumer is a good way to improve their satisfaction and gain customer orientation. However, what internal marketing strategies will have a positive effect on internal consumer satisfaction and customer orientation of private-owned sports center employees are still unclear. In this investigation, a total of 326 employees from the private-owned sports center were used to investigate the effects of internal marketing strategies on internal consumer satisfaction and customer orientation. All employees were asked to complete a questionnaire on 5-point scale. A path model was used to investigate the direct and indirect effects of hypothetical measurements on internal consumer satisfaction and customer orientation. The findings suggested that internal communication, administrative support, and educational training were important factors affecting internal consumer satisfaction and customer orientation. We concluded that the implementation of internal marketing strategies could improve internal consumer satisfaction and customer orientation, and higher levels of internal consumer satisfaction will encourage employees to have higher degrees of customer orientation. Therefore, the implementation of internal marketing strategy was beneficial to the development of private-owned sports centers.

Background and aimsThere is a demand for longitudinal studies that use both objective and subjective measures of physical activity to investigate the association of physical activity with the change in carotid intima-media thickness (CIMT). In order to investigate such association, we conducted an 8-year follow-up study that used both objective and subjective measures of physical activity.MethodsThis cohort study used subsamples of the ongoing Korean Genome and Epidemiology Study (KoGES). Included participants were between 49 to 79 years of age at baseline. Exclusion criteria included incomplete assessments of pedometer/accelerometer, international physical activity questionnaire (IPAQ), and baseline CIMT. Participants with a history of cardiovascular diseases were further excluded. Linear regression models were used for the main analysis. Age differences were assessed by stratifying the participants into < 60 years and ≥ 60 years.ResultsAfter removing excluded participants, 835 participants were included in the final analysis (age, 59.84 ± 6.53 years; 326 (39.04%) males). 453 participants were < 60 years and 382 participants were ≥ 60 years. The daily total step count was inversely associated with the percent change in overall CIMT over 8-years (β = -0.015, standard error = 0.007, P = 0.034). This association was present among participants in the < 60-year-old group (β = -0.026, standard error = 0.010, P = 0.006), but not among participants in the ≥ 60-year-old group (β = -0.010, standard error = 0.011, P = 0.38).ConclusionsThe findings suggest that taking preemptive actions of increasing physical activity may prevent the incidence of atherosclerosis.

Due to environmental and ecological changes and suitable habitats, the occurrence of vector-borne diseases is increasing. We investigated the seroprevalence of four major vector-borne pathogens in human patients with febrile illness who were clinically suspected of having Scrub Typhus (ST) caused by Orientia tsutsugamushi. A total of 187 samples (182 patient whole blood and sera samples, including 5 follow-up) were collected. Antibodies to Anaplasma phagocytophilum, Ehrlichia chaffeensis, Borrelia burgdorferi, and Bartonella henselae were tested by using indirect immunofluorescence assays. Molecular diagnoses were performed using real-time PCR. Of the 182 cases, 37 (20.3%) cases were designated as confirmed cases of ST, and the remaining 145 (79.7%) cases as other febrile diseases (OFDs). The seroprevalence of A. phagocytophilum, E. chaffeensis, B. burgdorferi, and B. henselae was 51.4% (19/37), 10.8% (4/37), 86.5% (32/37), and 10.8% (4/37) among the ST group, and 42.8% (62/145), 10.4% (19/145), 57.7% (105/145), and 15.9% (29/145) among the OFD group, respectively. There were no significant differences in the seroprevalence between the ST and the OFD groups. Considering the co-occurrence, 89.0% (162/182) had at least one antibody to tick-borne pathogens, 37.0% (60/162) were positive for two pathogens, 17.3% (28/162) for three pathogens, and 6.2% (10/162) for four pathogens. In real-time PCR, O. tsutsugamushi was positive in 16 cases [15 (40.5%) in ST group and 1 (2.2%) in OFD group], and the four other pathogens were negative in all cases except one confirmed as anaplasmosis. In evaluating the five follow-up samples, the appearance of new antibodies or an increase in the pre-existing antibody titers was detected. Our data highlighted that acute febrile illness and manifestations suggestive of a vector-borne infection must be recognized and further considered for coinfections in clinical practice and the laboratory.

Facility cultivation has been evolved from greenhouses to smart farms using artificial intelligence (AI) that simulates big data to maximize production. However, the big data for AI in smart farm is not studied well; the effect of differences among varieties within a crop remains unclear. Therefore, the response of two varieties of blueberry, 'Suziblue' and 'Star', to light was tested using SAPD meter in order to demonstrate the environmental responses could be different among varieties within the same species. The results showed that those two varieties had significant differences in SPAD values based on the leaf's position and time, whereas 'Star' did not. This indicates that the effect of light depends on the variety, which implies that other traits and other crops may show similar differences. These results are based on a simple experiment. However, it is enough to elucidate that it is extremely important to characterize responses to the environment not only for each crop but also for each variety to collect data for smart farming to increase accuracy for modeling; consequently, to maximize the efficiency of these facilities.

Aim Data on the use of non-vitamin K antagonist oral anticoagulants (NOACs) in relation to the risk of cardiovascular (CV) disease and renal protection among patients with atrial fibrillation (AF), are relatively sparse. We aimed to compare the effectiveness and safety of NOACs with those of warfarin for vascular protection in a large-scale, nationwide Asian population with AF. Methods and results Patients with AF who were prescribed oral anticoagulants according to the Korean Health Insurance Review and Assessment database between 2014 and 2017 were analyzed. The warfarin and NOAC groups were balanced using propensity score weighting. Clinical outcomes included ischemic stroke, myocardial infarction, angina pectoris, peripheral artery disease, chronic kidney disease (CKD), end-stage renal disease (ESRD), CV death, and all-cause death. NOAC use was associated with a lower risk of angina pectoris (HR, 0.79 [95% CI, 0.69–0.89] pConclusion NOACs were associated with a significantly lower risk of adverse CV and renovascular outcomes than warfarin in patients with AF.

To investigate the CGE on hair growth and to explore the mechanism that is involved in the acceleration of anagen induction, we investigated the effects of CGE studied on cell proliferation and molecular mechanism in human hair dermal papilla cells (hDPCs) and keratinocytes (HaCaT cells). Additionally, hair growth evaluation was carried out following topical treatment of the dorsal skin of telogen C57BL/6 mice with CGE for 14 days. As result, CGE increased cell viability and ALP activity in hDPCs. Moreover, CGE increased the expression of catenin beta 1 (CTNNB1), ALP, sex-determining region Y-box 2 (SOX2), insulin-like growth factor 1 (IGF1), and vascular endothelial growth factor A (VEGFA) genes in hDPCs. CGE increased the expression of proteins such as ALP, β-catenin, and phosphorylation of glycogen synthase kinase 3β (pGSK3β), and protein kinase B (pAKT) in hDPCs. Furthermore, CGE induced the proliferation of HaCaT cells and up-regulated AKT-ERK-GSKβ-β-catenin signaling in HaCaT cells. Additionally, the anagen induction effects of CGE were confirmed on the telogen-anagen transition mice model. these findings demonstrated that CGE promoted the entering the growth phase of hair follicle via activation of β-catenin signaling pathways in vivo. Thus, this study suggests that CGE might be a potential therapeutic reagent for hair growth.

Identification of 3D cephalometric landmarks that serve as proxy to the shape of human skull is the fundamental step in cephalometric analysis. Since manual landmarking from 3D computed tomography (CT) images is a cumbersome task even for the trained experts, automatic 3D landmark detection system is in a great need. Recently, automatic landmarking of 2D cephalograms using deep learning (DL) has achieved great success, but 3D landmarking for more than 80 landmarks has not yet reached a satisfactory level, because of the factors hindering machine learning such as the high dimensionality of the input data and limited amount of training data due to the ethical restrictions on the use of medical data. This paper presents a semi-supervised DL method for 3D landmarking that takes advantage of anonymized landmark dataset with paired CT data being removed. The proposed method first detects a small number of easy-to-find reference landmarks, then uses them to provide a rough estimation of the all landmarks by utilizing the low dimensional representation learned by variational autoencoder (VAE). The anonymized landmark dataset is used for training the VAE. Finally, coarse-to-fine detection is applied to the small bounding box provided by rough estimation, using separate strategies suitable for the mandible and the cranium. For mandibular landmarks, patch-based 3D CNN is applied to the segmented image of the mandible (separated from the maxilla), in order to capture 3D morphological features of mandible associated with the landmarks. We detect 6 landmarks around the condyle all at once rather than one by one, because they are closely related to each other. For cranial landmarks, we again use the VAE-based latent representation for more accurate annotation. In our experiment, the proposed method achieved a mean detection error of 2.88 mm for 90 landmarks using only 15 paired training data.

This study aimed to evaluate image quality, the detection rate of enlarged lymph nodes, and radiation dose exposure of ultralow-dose and low-dose abdominopelvic computed tomography (CT) in patients with lymphoma. Patients with lymphoma who underwent abdominopelvic CT using dual-source scanner were retrospectively recruited from a single center. CT images were obtained at 90 kVp dual-source mode reformatted in three data sets using the advanced modelled iterative reconstruction algorithm: 100% (standard-dose CT), 66.7% (low-dose CT), and 33.3% (ultralow-dose CT). Two radiologists analyzed subjective image quality and detection of abdominal enlarged lymph nodes on ultralow-dose, low-dose, and standard-dose CT blindly and independently. The results were compared with reference standards. Three readers (two radiologists and one hematologist) reviewed overall image quality and spleen size. In total, 128 consecutive CT scans (77 complete response, 44 partial response, 6 progressive disease, and 1 initial evaluation) from 86 patients (64 B-cell lymphoma, 14 T/NK-cell lymphoma, and 8 Hodgkin's lymphoma cases) were assessed. The enlarged lymph node-based detection rates for two readers were 97.0% (96/99) and 94.0% (93/99) on standard-dose CT, 97.0% (96/99) and 94.0% (93/99) on low-dose CT, and 94.0% (93/99) and 89.9% (89/99) on ultralow-dose CT. Overall image quality was 3.8 ± 0.5, 3.9 ± 0.5, and 4.1 ± 0.5 on ultralow-dose CT; 4.7 ± 0.4, 4.6 ± 0.5, and 4.8 ± 0.3 on low-dose CT; and 4.8 ± 0.4, 4.7 ± 0.4, and 4.9 ± 0.2 on standard-dose CT, according to two radiologists and one hematologist, respectively. Intraclass correlation coefficients of spleen size were 0.90 (95% confidence interval [CI], 0.87-0.93), 0.91 (95% CI, 0.88-0.93), and 0.91 (95% CI, 0.88-0.93) on ultralow-dose, low-dose, and standard-dose CT, respectively. Mean effective radiation doses of standard-dose, low-dose, and ultralow-dose CT were 5.7 ±1.8 mSv, 3.8 ± 1.2 mSv, and 1.9 ± 0.6 mSv, respectively. Our findings suggest that ultralow-dose and low-dose CT, even with radiation doses reduced by 66.7% and 33.3%, respectively, maintained adequate image quality. These imaging modalities may be employed for follow-up lymphoma evaluation in consideration of the long surveillance periods.

Multidomain lifestyle modification is considered an effective intervention for dementia prevention due to its multifactorial nature. Recognizing that participants' activity adherence is crucial for successful lifestyle modification, our team developed a smartphone application to enhance motivation toward brain health behavior based on gamification theory, which influences behaviors by enhancing motivation. The developed smartphone application has two main functions: delivering supporting videos from family, friends, and medical staff, and self-evaluation. We assessed the effectiveness of this smartphone application with regard to brain health behavior. In this eight-week randomized controlled trial, 40 participants were randomly assigned to the smartphone application intervention group or control group. The primary outcome reflected participants' brain health behavior in three categories: physical activity, cognitive activity, and healthy diet. Each brain health behavior was measured by the Korean version of the Global Physical Activity Questionnaire, Cognitive Activity Score, and Mediterranean DASH Intervention for Neurodegenerative Delay Diet Score. Furthermore, we investigated the change in motivation, measured by the Situational Motivation Scale. Additionally, we reviewed participants' self-record diary during the first, fourth, and eighth week of intervention for evaluation of adherence. The intervention group was found to have a positive association with moderate metabolic equivalent activities (P = 0.01) and intrinsic motivation change (P = 0.01). There was a significant difference between the intervention and control groups regarding average physical activity at week 8 (P = 0.037). An eight-week intervention with the smartphone application induced physical activity of moderate intensity through intrinsic motivation enhancement. We suggest that the motivation enhancement application could be an efficient option for maintaining and promoting psychosocial health behavior. This smartphone application can be applied to any other disease that needs behavioral change. Through the application, a broader spectrum of the population, regardless of time, space, and human resources, can benefit from community health services. Trial registration: Korean National Clinical Trial Registry CRIS identifier: KCT0005231.

AimsThe incidence and mortality of hepatocellular carcinoma (HCC) have decreased over time in South Korea, where hepatitis B virus (HBV) in endemic. This study investigated the changes in the characteristics and clinical outcomes of HCC patients in Korea.MethodsPatients initially diagnosed with HCC and treated at the National Cancer Center, Korea between 2000 and 2015 (n = 4,291) were followed up until February 2017. Differences in patient characteristics and outcomes were compared between chronological cohorts: cohort A (2000-2004, n = 1,157) vs. B (2005-2009, n = 1,678) vs. C (2010-2015, n = 1,456).ResultsThe median age of the patient cohort was 57 years (range, 13-98 years), and male predominance was noted (81.6%). HBV infection was the most common etiology (74.8%). The proportion of patients diagnosed with good liver function and small tumors (ConclusionsThe survival of patients with HCC, especially HBV-related HCC, has improved significantly over time in Korea.

Introduction Inter-hospital transfer (IHT) and primary percutaneous coronary intervention (PCI) are preferred over onsite thrombolysis when provided expeditiously. On the other hand, its benefit has not been evaluated in a real-world situation. This study examined the effects of IHT on the short- and long-term mortality in patients with acute myocardial infarction (AMI) and compared the reperfusion treatments and resources between the referring and receiving hospitals. Methods Patients newly diagnosed with AMI and admitted to hospital were selected from the national health insurance database from 2004 to 2018. The 30-day and one-year mortality in the transferred and non-transferred patients were estimated and compared using stabilized inverse probability of treatment weighting to account for confounding bias. Results Of the 258,291 participants, 10,158 were transferred to one or more hospitals. IHT was more likely to occur to older or more comorbid people, patients in rural areas, and those whose insurance was medical aid. The 30-day and one-year mortality of the non-IHT group was 9.7% and 15.8%, respectively, whereas the figure was 11.4% and 20.5% in the IHT group. After balancing the baseline characteristics, the transferred patients were 1.12 (95% CI: 1.06–1.20) and 1.25 (95% CI: 1.20–1.31) times more likely to die during the subsequent 30 days and one year, respectively, than those treated solely at the presenting hospital. In ST-segment elevation myocardial infarction (STEMI), the hazard ratios of the 30-day and 1-year mortality were 1.14 (95% CI: 0.97–1.35) and 1.31 (95% CI: 1.15–1.49) in the transferred patients after balancing cardiogenic shock and cardiac arrest. On-site thrombolysis was rarely performed in the referring hospitals. Conclusion Patients transferred for the treatment of AMI experienced higher short- and long-term mortality. Therefore, onsite thrombolysis and the estimated time delay to PCI should be considered in regional hospitals to reduce mortality with the organization of STEMI treatment networks.

Background/aimsWe measured the association between underlying chronic hepatitis B (CHB) and antiviral use with infection rates among patients who underwent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing.MethodsIn total, 204,418 patients who were tested for SARS-CoV-2 between January and June 2020 were included. For each case patient (n = 7,723) with a positive SARS-CoV-2 test, random controls (n = 46,231) were selected from the target population who had been exposed to someone with coronavirus disease 2019 (COVID-19) but had a negative SARS-CoV-2 test result. We merged claim-based data from the Korean National Health Insurance Service database collected. Primary endpoints were SARS-CoV-2 infection and severe clinical outcomes of COVID-19.ResultsThe proportion of underlying CHB was lower in COVID-19 positive patients (n = 267, 3.5%) than in COVID-19 negative controls (n = 2482, 5.4%). Underlying CHB was associated with a lower SARS-CoV-2 positivity rate, after adjusting for comorbidities (adjusted odds ratio [aOR] 0.65; 95% confidence interval [CI], 0.57-0.74). Among patients with confirmed COVID-19, underlying CHB tended to confer a 66% greater risk of severe clinical outcomes of COVID-19, although this value was statistically insignificant. Antiviral treatment including tenofovir and entecavir was associated with a reduced SARS-CoV-2 positivity rate (aOR 0.49; 95% CI, 0.37-0.66), while treatment was not associated with severe clinical outcomes of COVID-19.ConclusionsUnderlying CHB and antiviral agents including tenofovir decreased susceptibility to SARS-CoV-2 infection. HBV coinfection did not increase the risk of disease severity or lead to a worse prognosis in COVID-19.

BACKGROUND:The unique characteristics of long-term care facilities (LTCFs) including host factors and living conditions contribute to the spread of contagious pathogens. Control measures are essential to interrupt the transmission and to manage outbreaks effectively. AIM:The aim of this systematic review was to verify the causes and problems contributing to transmission and to identify control measures during outbreaks in LTCFs. METHODS:Four electronic databases were searched for articles published from 2007 to 2018. Articles written in English reporting outbreaks in LTCFs were included. The quality of the studies was assessed using the risk-of-bias assessment tool for nonrandomized studies. FINDINGS:A total of 37 studies were included in the qualitative synthesis. The most commonly reported single pathogen was influenza virus, followed by group A streptococcus (GAS). Of the studies that identified the cause, about half of them noted outbreaks transmitted via person-to-person. Suboptimal infection control practice including inadequate decontamination and poor hand hygiene was the most frequently raised issue propagating transmission. Especially, lapses in specific care procedures were linked with outbreaks of GAS and hepatitis B and C viruses. About 60% of the included studies reported affected cases among staff, but only a few studies implemented work restriction during outbreaks. CONCLUSIONS:This review indicates that the violation of basic infection control practice could be a major role in introducing and facilitating the spread of contagious diseases in LTCFs. It shows the need to promote compliance with basic practices of infection control to prevent outbreaks in LTCFs.

BackgroundThe development of deep learning (DL) algorithms is a three-step process-training, tuning, and testing. Studies are inconsistent in the use of the term "validation", with some using it to refer to tuning and others testing, which hinders accurate delivery of information and may inadvertently exaggerate the performance of DL algorithms. We investigated the extent of inconsistency in usage of the term "validation" in studies on the accuracy of DL algorithms in providing diagnosis from medical imaging.Methods and findingsWe analyzed the full texts of research papers cited in two recent systematic reviews. The papers were categorized according to whether the term "validation" was used to refer to tuning alone, both tuning and testing, or testing alone. We analyzed whether paper characteristics (i.e., journal category, field of study, year of print publication, journal impact factor [JIF], and nature of test data) were associated with the usage of the terminology using multivariable logistic regression analysis with generalized estimating equations. Of 201 papers published in 125 journals, 118 (58.7%), 9 (4.5%), and 74 (36.8%) used the term to refer to tuning alone, both tuning and testing, and testing alone, respectively. A weak association was noted between higher JIF and using the term to refer to testing (i.e., testing alone or both tuning and testing) instead of tuning alone (vs. JIF 10: adjusted odds ratio 2.41, P = 0.089). Journal category, field of study, year of print publication, and nature of test data were not significantly associated with the terminology usage.ConclusionsExisting literature has a significant degree of inconsistency in using the term "validation" when referring to the steps in DL algorithm development. Efforts are needed to improve the accuracy and clarity in the terminology usage.

ObjectiveTo compare the radiation dose and the objective and subjective image quality of 80 kVp and 80/150 kVp with tin filter (80/Sn150 kVp) computed tomography (CT) in oncology patients.MethodsOne-hundred-and-forty-five consecutive oncology patients who underwent third-generation dual-source dual-energy CT of the abdomen for evaluation of malignant visceral, peritoneal, extraperitoneal, and bone tumor were retrospectively recruited. Two radiologists independently reviewed each observation in 80 kVp CT and 80/Sn150 kVp CT. Modified line-density profile of the tumor and contrast-to-noise ratio (CNR) were measured. Diagnostic confidence, lesion conspicuity, and subjective image quality were calculated and compared between image sets. The effective dose and size-specific dose estimate (SSDE) were calculated in the image sets.ResultsModified line-density profile analysis revealed higher attenuation differences between the tumor and normal tissue in 80 kVp CT than in 80/Sn150 kVp CT (127 vs. 107, P = 0.05). The 80 kVp CT showed increased CNR in the liver (8.0 vs. 7.6) and the aorta (18.9 vs. 16.3) than the 80/Sn150 kVp CT. The 80 kVp CT yielded higher enhancement of organs (4.9 ± 0.2 vs. 4.7 ± 0.4, PConclusionsThe 80 kVp CT reduced the radiation dose by 45.2% in oncology patients while showing comparable or superior image quality to that of 80/Sn150 kVp CT for abdominal tumor evaluation.

IntroductionThe Korean National Health Insurance revised its reimbursement criteria to expand coverage for anti-osteoporotic drug treatments in 2011 (expanding diagnostic criteria and the coverage period for anti-osteoporotic therapy) and 2015 (including osteoporotic fracture patients regardless of bone mineral density). We examined whether the two revisions contributed to an increase in the prescription rates of anti-osteoporotic drugs in Korea.MethodsWe used the Health Insurance Review and Assessment Service-National Patient Sample data from 2010 through 2016. A segmented regression analysis of interrupted time series was performed to assess changes in the monthly prescription rates of anti-osteoporotic drugs among women aged 50 or older, defined as the proportion of elderly women prescribed with anti-osteoporotic drugs.ResultsBoth the levels (i.e., abrupt jump or drop) and the trends (i.e., slope) of the prescription rates of anti-osteoporotic drugs in the general population, osteoporotic patients, and osteoporotic fracture patients showed no significant changes after the first revision. However, there was a significant increase in the trends in the general population (β = 0.0166, p = 0.0173) and in osteoporotic patients (β = 0.1128, p = 0.0157) after the second revision. Women aged 65 to 79 years were the most significantly increased group in terms of the treatment proportion after the second revision because the trend was significant after the second revision in all three study populations (β = 0.0300, 0.1212, 0.1392, respectively; p < 0.05).ConclusionsAlthough the two revisions expanded reimbursement coverage, only the second revision on reimbursing based on osteoporotic fracture regardless of bone mineral density was associated with increasing the proportion of post-menopausal women being treated with anti-osteoporotic drugs.

This study aimed to prospectively investigate the association between body weight (ΔBW) or body volume variations (ΔBV) and inter- or intra-fractional variations (Δ(inter) or Δ(intra)) in patients with head and neck cancer (HNC) undergoing radiotherapy (RT). This study enrolled patients with HNC from December 2015 to December 2017. All patients underwent curative intensity-modulated RT (IMRT) either as definitive or adjuvant treatment. Six-dimensional inter- and intra-fractional variations (Δ(inter) and Δ(intra)) were obtained with ExacTrac (BrainLAB, Feldkirchen, Germany) system. BV was measured 7.5 cm cranio-caudally from the centre using cone beam computed tomography. The BW, BV, and Δ(inter) were calculated based on the value obtained on the first treatment day after each simulation. Both Δ(inter) and Δ(intra) were considered in calculating the optimal margins for planning target volume (PTV), which was calculated using van Herk's formula. In total, 678 fractions with 39 simulations in 22 patients were analysed. The average ΔBW and ΔBV was -0.43±1.90 kg (range, -7.3 to 5.0) and -24.34±69.0 cc (range, -247.15 to 214.88), respectively. In correlation analysis, Δ(intra) was more associated with ΔBW or ΔBV than Δ(inter). Receiver operating characteristic analysis showed Δ(intra) could differentiate ΔBW from ΔBV, while Δ(inter) could not. The optimal margins for PTV considering both Δ(inter) and Δ(intra) were 3.70 mm, 4.52 mm, and 5.12 mm for the right-left, superior-inferior, and anterior-posterior directions, respectively. In conclusion, the PTV margin of 6 mm for anterior-posterior direction and 5 mm for the other directions were needed. ΔBW or ΔBV correlated with Δ(intra) rather than Δ(inter). Therefore, ΔBW or ΔBV should be assessed for accurate IMRT in patients with HNC.

Spasticity is an important barrier that can hinder the restoration of function in stroke patients. Although several studies have attempted to elucidate the relationship between brain lesions and spasticity, the effects of specific brain lesions on the development of spasticity remain unclear. Thus, the present study investigated the effects of stroke lesions on spasticity in stroke patients. The present retrospective longitudinal observational study assessed 45 stroke patients using the modified Ashworth Scale to measure muscle spasticity. Each patient was assessed four times: initially (within 2 weeks of stroke) and at 1, 3, and 6 months after the onset of stroke. Brain lesions were analyzed using voxel-based lesion symptom mapping (VLSM) with magnetic resonance imaging images. Spasticity developed to a certain degree within 3 months in most stroke patients with spasticity. The VLSM method with non-parametric mapping revealed that lesions in the superior corona radiata, posterior limb of the internal capsule, posterior corona radiata, thalamus, putamen, premotor cortex, and insula were associated with the development of upper-limb spasticity. Additionally, lesions of the superior corona radiata, posterior limb of the internal capsule, caudate nucleus, posterior corona radiata, thalamus, putamen, and external capsule were associated with the development of lower-limb spasticity. The present study identified several brain lesions that contributed to post-stroke spasticity. Specifically, the involvement of white matter tracts and the striatum influenced the development of spasticity in the upper and lower limbs of stroke patients. These results may be useful for planning rehabilitation strategies and for understanding the pathophysiology of spasticity in stroke patients.

ObjectivesPostmicturition dribble (PMD) is a very common symptom in males with lower urinary tract symptoms (LUTS) worldwide, but there is no adequate questionnaire to assess it. Therefore, we developed a questionnaire named the Hallym Post Micturition Dribble Questionnaire (HPMDQ) to assess PMD, and the aim of this study is to validate it.MethodsA series of consecutive male patients newly diagnosed with LUTS and over 40 years of age who visited any of 5 medical institutions were included. LUTS were assessed in all patients using the International Prostate Symptom Score (IPSS), and PMD was assessed using the HPMDQ.ResultsIn total, 2134 male patients aged 40 to 91 years were included in this study. Of these patients, 1088 (51.0%) reported PMD. In the PMD group, the mean values for HPMDQ-Q1, HPMDQ-Q2, HPMDQ-Q3 and HPMDQ total score were 1.39, 1.10, 1.76 and 4.25, respectively. In the non-PMD group, the mean values of these scores were 0, 0.18, 1.52 and 1.58, respectively. The difference in HPMDQ scores between the 2 groups was statistically significant. PMD was significantly associated with the voiding symptoms of LUTS, prostate size and postvoid residual but not with storage symptoms.ConclusionsThe HPMDQ, which consists of 5 questions (frequency, severity, bother, quality of life and response to treatment for PMD), was developed, and its use for assessing PMD is validated in this study. It may be a useful tool for further research and in clinical practice for PMD.

ObjectiveResearch biopsies are an essential component of cancer clinical trials for studying drug efficacy and identifying biomarkers. Site-level clinical investigators, however, do not have access to results on the adequacy of research biopsies for histological or molecular assays, because samples are sent to central labs and the test results are seldom reported back to site-level investigators unless requested. We evaluated the feasibility, safety, and adequacy of research biopsies performed at an academic medical center.Materials and methodsWe retrospectively reviewed the data on 122 research biopsy sessions conducted in 99 patients via percutaneous core needle biopsy for 39 clinical trials from January 2017 to February 2018 at a single institute. We asked the sponsors of each clinical trial for the adequacy of the biopsy samples for histological or molecular assays.ResultsThe biopsy success rate was 93.4% (113/122), with nine samples categorized as inadequate for obtaining pathologic diagnosis. Post-biopsy complications occurred in 9.8% (12/122) of biopsies, all of which were mild and completely recovered by the day after the biopsy. The sponsors of clinical trials provided feedbacks on the adequacy of 76 biopsy samples, and noted that a total of 8 biopsy samples from 7 patients were inadequate for analysis, resulting in an adequacy rate of 89.5% (68/76): the reasons for inadequacy were insufficient tumor content for immunohistochemistry (n = 3) and low RNA yield for sequencing (n = 5).ConclusionResearch biopsies performed at an experienced, multidisciplinary center had acceptable safety for patients as well as practicality in terms of obtaining adequate tissue samples for molecular studies.

BackgroundGiven the complexity of managing hepatocellular carcinoma (HCC), a multidisciplinary approach (MDT) is recommended to optimize management of HCC patients. However, evidence suggesting that MDT improves patient outcome is limited.MethodsWe performed a retrospective cohort study of all patients newly-diagnosed with HCC between 2005 and 2013 (n = 6,619). The overall survival (OS) rates between the patients who were and were not managed via MDT were compared in the entire cohort (n = 6,619), and in the exactly matched cohort (n = 1,396).ResultsIn the entire cohort, the 5-year survival rate was significantly higher in the patients who were managed via MDT compared to that of the patients who were not (71.2% vs. 49.4%, P < 0.001), with an adjusted hazard ratio (HR) of 0.47 (95% confidence interval [CI]; 0.41-0.53). In the exactly matched cohort, the 5-year survival rate was higher in patients who were managed via MDT (71.4% vs. 58.7%, P < 0.001; HR [95% CI] = 0.67 [0.56-0.80]). The survival benefit of MDT management was observed in most pre-defined subgroups, and was especially significant in patients with poor liver function (ALBI grade 2 or 3), intermediate or advanced tumor stage (BCLC stage B or C), or high alphafetoprotein levels (≥200 ng/ml).ConclusionMDT management was associated with improved overall survival in HCC patients, indicating that MDT management can be a valuable option to improve outcome of HCC patients. This warrants prospective evaluations.

Convincing data that support routine use of preventive therapy against hepatitis B virus (HBV) reactivation in radiotherapy (RT) for hepatocellular carcinoma (HCC) are lacking. The aim of this study was to investigate the incidence, clinical significance, and risk factors of HBV reactivation after RT. Medical records of 133 HBsAg (+) HCC patients who received radiotherapy from March 2009 to February 2016 were reviewed. Patients were divided into two groups: 1) non-antiviral group, those who did not receive antiviral therapy before RT (n = 27); and antiviral group (those who underwent antiviral therapy before RT) (n = 106). Factors related to HBV reactivation in HCC patients were evaluated. 17 (12.7%) of 133 patients developed HBV reactivation after RT. Patients in the antiviral group had significantly lower rates of HBV reactivation than those in the non-antiviral group (7.5% vs. 33.3%, p

To our knowledge, little is known regarding whether white matter hyperintensities (WMH) affect the prognosis of cryptogenic stroke (CS) patients. Understanding this association may be helpful with expecting the prognosis of CS patients.This retrospective observational study enrolled consecutive CS patients who underwent brain MRI and comprehensive cardiac evaluation. Severe WMH was defined as Fazekas' score ≥3. We defined poor functional outcome as modified Rankin Scale score ≥3 at 3 months. Long-term mortality and causes of death were identified using national death certificates and assessed by Kaplan-Meier method and regression analysis model.Among 2732 patients with first-ever ischemic stroke, 599 (21.9%) patients were classified as having CS. After exclusions, 235 patients were enrolled and followed up for a median of 7.7 years (IQR, 6.7-9.0). Severe WMH were found in 81 (34.5%) patients. After adjustments, severe WMH were an independent predictor for poor functional outcomes at 3 months (OR 5.25, 95% CI, 2.07-13.31). Subgroup analysis showed that severe WMH were an independent predictor for long-term mortality only in younger patients (age < 65) (HR 3.11, 95% CI, 1.29-7.50), but not in older patients (HR 1.19, 95% CI, 0.63-2.23).Severe WMH were independently associated with short-term functional outcomes in CS patients and independently associated with long-term mortality in younger CS patients. Grading WMH is of value in predicting prognosis of CS patients with young age.

BACKGROUND:A wider angle between the left anterior descending coronary artery (LAD) and left circumflex coronary artery (LCX) has been suggested to induce plaque formation in the arterial system via changes in shear stress. However, the relationship between the left main coronary artery (LM)-LAD angle and LAD stenosis has not been investigated. Therefore, we aimed to evaluate the associations between the LM-LAD and LAD-LCX angles and LAD stenosis. METHODS:Coronary computed tomography angiographies (CTAs) of 201 patients with suspected coronary artery disease were analyzed. Angle measurements were performed twice by experts using CTA images, and the values were averaged. The patients were divided into two groups, based on the presence of significant LAD stenosis (luminal diameter narrowing ≥50%) on CTA. RESULTS:The mean LM-LAD and LAD-LCX angles were 37.46° and 63.04°, respectively. The LM-LAD and LAD-LCX angles of the group with significant LAD stenosis were significantly wider than that of the group with nonsignificant LAD stenosis (P

In the 2016-2017 season, the A(H3N2) influenza epidemic presented an unusual early peak pattern compared with past seasons in South Korea. The interim vaccine effectiveness (VE) of influenza vaccination in preventing laboratory-confirmed influenza was estimated using test-negative design through the tertiary hospital-based influenza surveillance system in South Korea. From 1 September, 2016 to 7 January, 2017, adjusted VE of influenza vaccination in preventing laboratory-confirmed A(H3N2) was -52.1% (95% confidence interval [CI], -147.2 to 6.4); -70.0% (95% CI, -212.0 to 7.4) in 19-64 years and 4.3% (95% CI, -137.8 to 61.5) in the elderly. Circulating A(H3N2) viruses belonged to the three phylogenetic subclades of 3C.2a, differently to A/Hong Kong/4801/2014, the current vaccine strain. Amino acid substitutions in hemagglutinin of circulating viruses seem to contribute to low VE. In conclusion, interim VE analysis presented that the protection of laboratory-confirmed influenza by seasonal influenza vaccination did not show the statistical significance in South Korea in the 2016-2017 influenza season.

Studies investigating the impact of white matter hyperintensities (WMHs) on the response of acetylcholinesterase inhibitors in patients with Alzheimer's disease (AD) have presented inconsistent results. We aimed to compare the effects of the rivastigmine patch between patients with AD with minimal WMHs and those with moderate WMHs.Three hundred patients with mild to moderate AD were enrolled in this multicenter prospective open-label study and divided into two groups. Group 1 comprised patients with AD with minimal WMHs and group 2 comprised those with moderate WMHs. The patients were treated with a rivastigmine patch for 24 weeks. Efficacy measures were obtained at baseline and after 24 weeks. The primary endpoint was the change in the AD Assessment Scale-Cognitive subscale (ADAS-Cog) from the baseline to the end of the study.Of the 300 patients, there were 206 patients in group 1 and 94 patients in group 2. The intention-to-treat group comprised 198 patients (group 1, n = 136; group 2, n = 46) during the 24-week study period. Demographic factors did not differ between group 1 and group 2. There were no significant differences in change in ADAS-cog between group 1 (-0.62±5.70) and group 2 (-0.23±5.98) after the 24-week rivastigmine patch therapy (p = 0.378). The patients in group 1 had a 0.63-point improvement from baseline on the Frontal Assessment Battery, while group 2 had a 0.16-point decline compared to baseline at the end of the study (p = 0.037). The rates of adverse events (AEs) (42.6 vs. 40.3%) and discontinuation due to AEs (10.3% vs. 4.3%) did not differ between the groups.Although the efficacy and tolerability of rivastigmine patch therapy were not associated with WMH severity in patients with AD, some improvement in frontal function was observed in those with minimal WMHs.ClinicalTrials.gov NCT01380288.

The Grading system for Adrenal Pheochromocytoma and Paraganglioma (GAPP) was proposed for predicting the metastatic potential of pheochromocytoma and paraganglioma to overcome the limitations of the Pheochromocytoma of the Adrenal Scaled Score (PASS). However, to date, no study validating the GAPP has been conducted, and previous studies did not include mutations in the succinate dehydrogenase type B (SDHB) gene in the score calculation. In this retrospective cohort study, we validated the prediction ability of GAPP and assessed whether it would be improved by inclusion of the loss of SDHB immunohistochemical staining.We divided the tumors into non-metastatic and metastatic groups based on the presence of synchronous or metachronous metastases. The GAPP score and PASS at the initial operation were measured. Moreover, we combined some GAPP parameters with the immunohistochemical staining of SDHB to obtain a modified GAPP (M-GAPP) score.Metastasis occurred in 15/72 (20.8%) patients, with a mean follow-up of 43.5 months. Loss of SDHB staining was more frequent (P = 0.044) in the metastatic group. The GAPP score (P = 0.006), PASS (P = 0.003), and M-GAPP score (P

The presence of white matter hyperintensity (WMH) is related to poor long-term outcomes in stroke patients. However, the long-term outcome is unknown in patients with both large artery atherosclerosis (LAA) and WMH.We investigated the impact of WMH on long-term outcome in patients with LAA. Consecutive patients in a prospective stroke registry were included. Patients were followed for a median of 7.7 years (interquartile range, 5.6-9.7). The degree of WMH was assessed by Fazekas grade on fluid-attenuated inversion recovery images. Total WMH burden was calculated by summation of Fazekas scores in periventricular and deep white matter. Severe WMH was defined as total burden score ≥ 3.Among 2529 patients, 639 patients (25.3%) were classified with the LAA subtype. After applying exclusion criteria, the data from 538 patients were analyzed. The mean patient age was 65.7 ± 10.3 years. Severe WMHs were found in 243 patients (45.2%). During follow-up, 200 patients (37.2%) died. Cox regression analysis showed that LAA patients with severe WMH had a 1.50-fold (95% CI, 1.12-2.00, p = 0.007) higher death rate compared to those without. In the older age group (≥65 years), Cox regression revealed that patients with severe WMH had a 1.75-fold (95% CI, 1.15-2.65, p = 0.008) higher 5-year death rate, whereas the younger age group did not have this association.The degree of WMH might be a surrogate marker for long-term outcome in patients with LAA. Atherosclerotic burdens in both small and large arteries might impact long-term prognosis in ischemic stroke patients.

Reactive oxygen species modulator-1 (Romo1) is a novel protein that has been reported to be crucial for cancer cell proliferation and invasion. However, its clinical implications in colorectal cancer patients are not well-known. For the first time, we investigated the association between Romo1 and the clinical outcomes of colorectal cancer patients.We examined Romo1 expression in resected tumor tissues immunohistochemically and assessed it with histological scores. We conducted survival analyses for patients who had curative resection (n = 190) in accordance with clinical parameters including level of Romo1 expression, and we examined the association between Romo1 expression and cell invasion using Matrigel invasion assay in colorectal cancer cells.We observed significantly longer mean disease-free survival in the low Romo1 group compared with the high Romo1 group (161 vs 127.6 months, p = 0.035), and the median overall survival of the low Romo1 group was significantly longer than that of the high Romo1 group (196.9 vs 171.3 months, p = 0.036). Cell invasiveness decreased in the Romo1 knockdown colorectal cancer cells in contrast to the controlled cells. Romo1 overexpression in tumor tissue was associated with a high lymph node ratio between the metastatic and examined lymph nodes (p = 0.025).Romo1 overexpression in tumor tissue was significantly associated with survival in curatively resected colorectal cancer patients, suggesting Romo1 expression as a potential adverse prognostic marker. Increased Romo1 expression was found to be associated with high lymph node ratio. Cancer invasiveness appeared to be a key reason for the poor survival related to highly expressed Romo1.

This study aimed to evaluate the relationship between insulin resistance and the bone mineral density (BMD) of femur and lumbar spine in Korean adults who are expected to exhibit near peak bone mass.Data from the Korean National Health and Nutrition Examination Survey 2008-2010 were analyzed. A total of 2,750 participants aged 25-35 years were included. Insulin resistance was assessed using a homeostatic model assessment of insulin resistance (HOMA-IR) and serum fasting insulin.In a multivariate linear regression analysis, the HOMA-IR was significantly inversely associated with the BMD of the total hip (TH, β = -0.052, P = 0.002), femoral neck (FN, β = -0.072, P

Birt-Hogg-Dube syndrome (BHD) is a rare disorder caused by mutations in the gene that encodes folliculin (FLCN) and is inherited in an autosomal dominant manner. BHD is commonly accompanied by fibrofolliculomas, renal tumors, multiple pulmonary cysts, and spontaneous pneumothorax. The aim of this study was to detect BHD prospectively in patients undergoing chest computed tomography (CT) scans and to evaluate further the characteristics of BHD in Korea.We prospectively checked and reviewed the chest CT scans obtained for 10,883 patients at Gangnam Severance Hospital, Seoul, Korea, from June 1, 2015 to May 31, 2016. Seventeen patients met the study inclusion criteria and underwent screening for FLCN mutation to confirm BHD. We analyzed the characteristics of the patients confirmed to have BHD and those for a further 6 patients who had previously been described in Korea.Six (0.06%) of the 10,883 patients reviewed were diagnosed with BHD. There was no difference in demographic or clinical features between the patients with BHD (n = 6) and those without BHD (n = 11). Pneumothorax was present in 50% of the patients with BHD but typical skin and renal lesions were absent. The maximum size of the cysts in the BHD group (median 39.4 mm; interquartile range [IQR] 11.4 mm) was significantly larger than that in the non-BHD group (median 15.8 mm; IQR 7.8 mm; P = 0.001). Variable morphology was seen in 100.0% of the cysts in the BHD group but in only 18.2% of the cysts in the non-BHD group (P = 0.002). Nine (95%) of the total of 12 Korean patients with BHD had experienced pneumothorax. Typical skin and renal lesions were present in 20.0% of patients with BHD.Our findings suggest that BHD can be detected if chest CT scans are read in detail.

Sarcopenia is a common syndrome in chronic diseases such as liver cirrhosis. The association between sarcopenia and outcomes, such as complications and survival has recently been described in various patient groups. However, study results remain inconclusive. Therefore, the aim of this study was to systematically review the impact of sarcopenia on outcome in patients with cirrhosis.We conducted a systematic review (SR) and meta-analysis (MA) on the impact of sarcopenia on outcome in liver cirrhosis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Of the 312 studies identified, 20 were eligible according to our inclusion criteria. Most of the studies used CT to diagnose sarcopenia. Two studies used bioelectrical impedance analysis (BIA), 10 studies used skeletal muscle index (SMI) and 8 studies used total psoas muscle area (TPA). Seven studies included Asian participants and the remaining 13 studies included Western participants. The prevalence rate of sarcopenia among participants was mean 48.1%, and appeared more among men with a rate of 61.6% whereas the rate was 36% for women. With respect to clinical outcomes, patients with sarcopenia had poorer survival rates and an increased risk of complications such as infection compared to those without sarcopenia. According to the analysis of race subgroup, Asians had a HR 2.45 (95% confidence interval (CI) = 1.44-4.16, P = 0.001) of mortality whereas Westerners had a HR 1.45 (95% CI = 1.002-2.09, P

[This corrects the article DOI: 10.1371/journal.pone.0174160.].

We aimed to evaluate the predictive power of longitudinal and circumferential fibers according to left ventricular ejection fraction (LVEF) in successfully reperfused acute ST elevation myocardial infarction (STEMI) patients.Total 691 patients (age 59±13, 20% female) underwent clinical evaluation and conventional and strain echocardiography (Global longitudinal strain (GLS), global circumferential strain (GCS)). The clinical outcome was defined as the composite of death, hospitalization for heart failure, non-fatal myocardial infarction, and ventricular arrhythmia.During a follow-up of 39±19 months, there were 47 (6.8%) clinical events. In multivariate Cox models adjusted clinical risk factors, age (HR 1.08, p = 0.001) and GLS (HR 1.37, p = 0.001) were independent predictors. The addition of GLS resulted in significant incremental improvement in the predictive value on LVEF (χ2 = 31.8→45.8, p50%), GLS, GCS and LVEF did not show significant predictive power.GLS is a most powerful predictor of outcome in successfully reperfused STEMI patients, especially with depressed LV dysfunction, although GCS and LVEF lost their predictive power for the patients with significantly depressed LV function. However, GLS did not predict outcome for the patients with preserved LVEF (>50%).

PURPOSE:We investigated the association of the macular ganglion cell-inner plexiform layer (GCIPL) and peripapillary retinal nerve fiber layer (RNFL) thicknesses with disease progression in mild cognitive impairment (MCI) and Alzheimer's disease (AD). METHODS:We recruited 42 patients with AD, 26 with MCI, and 66 normal elderly controls. The thicknesses of the RNFL and GCIPL were measured via spectral-domain optic coherent tomography in all participants at baseline. The patients with MCI or AD underwent clinical and neuropsychological tests at baseline and once every year thereafter for 2 years. RESULTS:The Clinical Dementia Rating scale-Sum of Boxes (CDR-SB) score exhibited significant negative relationships with the average GCIPL thickness (β = -0.15, p < 0.05) and the GCIPL thickness in the superotemporal, superonasal, and inferonasal sectors. The composite memory score exhibited significant positive associations with the average GCIPL thickness and the GCIPL thickness in the superotemporal, inferonasal, and inferotemporal sectors. The temporal RNFL thickness, the average and minimum GCIPL thicknesses, and the GCIPL thickness in the inferonasal, inferior, and inferotemporal sectors at baseline were significantly reduced in MCI patients who were converted to AD compared to stable MCI patients. The change of CDR-SB from baseline to 2 years exhibited significant negative associations with the average (β = -0.150, p = 0.006) and minimum GCIPL thicknesses as well as GCIPL thickness in the superotemporal, superior, superonasal, and inferonasal sectors at baseline. CONCLUSIONS:Our data suggest that macular GCIPL thickness represents a promising biomarker for monitoring the progression of MCI and AD.

Cardiac valvular calcification is associated with the overall coronary plaque burden and considered an independent cardiovascular risk and prognostic factor. The purpose of this study was to evaluate the relationship between the presence of valvular calcification and plaque morphology and/or vulnerability.Transthoracic echocardiography was used to assess valvular calcification in 280 patients with coronary artery disease who underwent radiofrequency intravascular ultrasound (Virtual Histology IVUS, VH-IVUS). A propensity score-matched cohort of 192 patients (n = 96 in each group) was analyzed. Thin-capped fibroatheroma (TCFA) was defined as a necrotic core (NC) >10% of the plaque area with a plaque burden >40% and NC in contact with the lumen for ≥3 image slices. A remodeling index (lesion/reference vessel area) >1.05 was considered to be positive.Patients were divided into two groups: any calcification in at least one valve (152 patients) vs. no detectable valvular calcification (128 patients). Groups were similar in terms of age, risk factors, clinical diagnosis, and angiographic analysis after propensity score-matched analysis. Gray-scale IVUS analysis showed that the vessel size, plaque burden, minimal lumen area, and remodeling index were similar. By VH-IVUS, % NC and % dense calcium (DC) were greater in patients with valvular calcification (p = 0.024, and p = 0.016, respectively). However, only % DC was higher at the maximal NC site by propensity score-matched analysis (p = 0.029). The frequency of VH-TCFA occurrence was higher depending on the complexity (p = 0.0064) and severity (p = 0.013) of valvular calcification.There is a significant relationship between valvular calcifications and VH-IVUS assessment of TCFAs. Valvular calcification indicates a greater atherosclerosis disease complexity (increased calcification of the coronary plaque) and vulnerable coronary plaques (higher incidence of VH-TCFA).

Infrared (IR) spectroscopy has been used to quantify chemical and structural characteristics of a wide range of materials including biological tissues. In this study, we examined spatial changes in the chemical characteristics of rat retina in response to intraocular pressure (IOP) elevation using synchrotron infrared microscopy (SIRM), a non-destructive imaging approach. IOP elevation was induced by placing a suture around the eye of anaesthetised rats. Retinal sections were collected onto transparent CaF2 slides 10 days following IOP elevation. Using combined SIRM spectra and chemical mapping approaches it was possible to quantify IOP induced changes in protein conformation and chemical distribution in various layers of the rat retina. We showed that 10 days following IOP elevation there was an increase in lipid and protein levels in the inner nuclear layer (INL) and ganglion cell layer (GCL). IOP elevation also resulted in an increase in nucleic acids in the INL. Analysis of SIRM spectra revealed a shift in amide peaks to lower vibrational frequencies with a more prominent second shoulder, which is consistent with the presence of cell death in specific layers of the retina. These changes were more substantial in the INL and GCL layers compared with those occurring in the outer nuclear layer. These outcomes demonstrate the utility of SIRM to quantify the effect of IOP elevation on specific layers of the retina. Thus SIRM may be a useful tool for the study of localised tissue changes in glaucoma and other eye diseases.