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The object of this study was to evaluate the factors affecting quality of life in parents with type 1 diabetes children. The design of this study was a cross-sectional survey. The participants of the study were 147 parents with type 1 diabetes children and data collection was conducted online survey. The data were analyzed by correlation and multiple regression analysis. The mean age of the participants was 40.65±5.22 year, female was 116 (78.9%), and there were 89 cases of two children. The total scores of quality of life in parents with type 1 diabetes children was 60.19±16.24 (range: 15.97~95.83) and diabetes family conflict scores was 27.35±6.09 (range: 19.00~57.00). The explanatory power of the quality of life in parents with type 1 diabetes children model which was constructed by three variables of gender of children, duration of disease, and diabetes family conflict was 25.0% (F=17.15, p

The AHNAK nucleoprotein has been determined to exert an anti-obesity effect in adipose tissue and further inhibit adipogenic differentiation. In this study, we examined the role of AHNAK in regulating hepatic lipid metabolism to prevent diet-induced fatty liver. Ahnak KO mice have reportedly exhibited reduced fat accumulation in the liver and decreased serum triglyceride (TG) levels when provided with either a normal chow diet or a high-fat diet (HFD). Gene expression profiling was used to identify novel factors that could be modulated by genetic manipulation of the Ahnak gene. The results revealed that fibroblast growth factor 21 (FGF21) was markedly increased in the livers of Ahnak KO mice compared with WT mice fed a HFD. Ahnak knockdown in hepatocytes reportedly prevented excessive lipid accumulation induced by palmitate treatment and was associated with increased secretion of FGF21 and the expression of genes involved in fatty acid oxidation, which are primarily downstream of PPARα. These results indicate that pronounced obesity and hepatic steatosis are attenuated in HFD-fed Ahnak KO mice. This may be attributed, in part, to the induction of FGF21 and regulation of lipid metabolism, which are considered to be involved in increased fatty acid oxidation and reduced lipogenesis in the liver. These findings suggest that targeting AHNAK may have beneficial implications in preventing or treating hepatic steatosis., Liver disease: A potential treatment for nonalcoholic fatty liver A protein that modulates lipid accumulation could be a target for controlling nonalcoholic fatty liver disease (NAFLD). The AHNAK protein regulates fat cell development, and mice lacking AHNAK are less susceptible to obesity after being fed a HFD. South Korean researchers led by Je Kyung Seong of Seoul National University and Yun Soo Bae of Ewha Womans University, Seoul, have identified a mechanism by which AHNAK inhibition prevents lipid accumulation in NAFLD. The authors profiled gene expression in AHNAK-deficient mice, and noted a striking increase in levels of a signaling protein called FGF21 in the liver. This elevated FGF21 was in turn linked to increased breakdown and reduced production of fatty acids. Therapeutic interventions that inhibit AHNAK could help control NAFLD, a hard-to-treat condition that can ultimately lead to cirrhosis and liver failure.

Metabolic syndrome (MS) is diagnosed using absolute criteria that do not consider age and sex, but most studies have shown that the prevalence of MS increases with age in both sexes. Thus, the evaluation of MS should consider sex and age. We aimed to develop a new index that considers the age and sex for evaluating an individual’s relative overall MS status. Data of 16,518,532 subjects (8,671,838 males and 7,846,694 females) who completed a validated health survey of the National Health Insurance Service of the Republic of Korea (2014‒2015) were analyzed to develop an MS-biological age model. Principal component score analysis using waist circumference, pulse pressure, fasting blood sugar, triglyceride levels, and high-density lipoprotein level, but not age, as independent variables were performed to derive an index of health status and biological age. In both sexes, the age according to the MS-biological age model increased with rising smoking and alcohol consumption habits and decreased with rising physical activity. Particularly, smoking and drinking affected females, whereas physical activity affected males. The MS-biological age model can be a supplementary tool for evaluating and managing MS, quantitatively measuring the effect of lifestyle changes on MS, and motivating patients to maintain a healthy lifestyle.

Purpose Emerging data suggest that higher radiation doses in post-mastectomy radiotherapy may be associated with an increased risk of reconstruction complications. This study aimed to validate previous findings regarding the impact of radiation dose on complications among women with breast cancer using a multi-center dataset. Methods Fifteen institutions participated, and women with breast cancer who received radiotherapy after either autologous or prosthetic breast reconstruction were included. The primary endpoint was major post-radiation therapy complications requiring re-operation for explantation, flap failure, or bleeding control. Results In total, 314 patients were included. Radiotherapy was performed using both conventional fractionation and hypofractionation in various schedules. The range of the radiation therapy dose in Equivalent Dose in 2 Gy fractions (EQD2; α/β = 3.5) varied from 43.4 to 71.0 Gy (median dose: 48.6 Gy). Boost radiation therapy was administered to 49 patients. Major post-radiation therapy complications were observed in 24 (7.6%) patients. In multivariate analysis, an increasing EQD2 per Gy (odds ratio [OR]: 1.58, 95% confidence interval [CI]: 1.26–1.98; p, Highlights • Radiation dose is associated with the risk of breast reconstruction complications. • We conducted a retrospective multi-center observational study of 314 women in Korea. • Complication-related risk factors were identified using multivariate analysis. • Use of hypofractionated radiation therapy may improve breast reconstruction outcomes. • A prospective multi-center study is under way to further validate our findings.

Acute promyelocytic leukemia (APL) is a type of acute myeloid leukemia characterized by predominating abnormal promyelocytes with a PML-RARA rearrangement or a variant thereof. BCR-ABL1 rearrangement is an oncogenic event that is usually associated with chronic myeloid leukemia but also occurs in both acute lymphoblastic and acute myeloid leukemias and in healthy individuals. However, APL with concurrent PML-RARA and BCR-ABL1 rearrangements has rarely been reported. Herein, we describe a patient with APL exhibiting a BCR-ABL1 rearrangement in a minor clone and discuss the importance of evaluating this genetic alteration in terms of pathogenesis and treatment.

Background To evaluate the usefulness of surveillance-abbreviated magnetic resonance imaging (AB-MRI) for the detection of ipsilateral local tumor recurrence (LTR) in patients who underwent oncoplastic breast-conserving surgery (BCS) with acellular dermal matrix (ADM) by comparing its diagnostic performance with that of mammography (MG) and ultrasonography (US). Methods The postoperative MG, US, and AB-MRI findings of the ipsilateral breast and pathological results of 324 patients who underwent oncoplastic BCS using ADM were reviewed. The cancer detection rate (CDR), sensitivity, specificity, positive predictive value (PPV) for biopsy, accuracy, and area under the curve (AUC) for each imaging modality were calculated. Results A total of 8 ipsilateral LTRs were diagnosed, and most cancers (87.5%) were stage 0 or 1 (median size of invasive cancer, 1.44 cm; range, 0.7–2 cm). The CDRs of MG, US, MG + US, and AB-MRI were 0.009, 0.012, 0.015, and 0.025 per woman, respectively. Three cancers were detectable on only AB-MRI, and the additional CDR of AB-MRI was 0.010. The sensitivity and specificity of MG, US, MG + US, and AB-MRI were 37.5%, 50%, 62.5%, and 100% and 99.7%, 98.4%, 98.1%, and 97.8%, respectively. The PPVs for biopsy were 75%, 44.4%, 45.5%, and 53.3%, respectively. The AUC was significantly higher for AB-MRI (0.989) than for MG alone (0.686, P = 0.0009), US alone (0.742, P = 0.009), and MG + US (0.803, P = 0.04). A total of 66.7% of cancers visible on only AB-MRI were located at the deep posterior portion of the excision cavity, which might have been missed with MG or MG + US due to masking by the ADM filler. Conclusion AB-MRI can improve the detection of ipsilateral LTR despite postoperative changes caused by ADM fillers compared to conventional MG and US. Patients who undergo BCS with ADM can be candidates for AB-MRI surveillance considering improved cancer detection and high sensitivity.

To compare the performance of margin assessment of specimen mammography (SM) in patients with breast-conserving surgery (BCS) on mobile devices and 5-megapixel (5M) thin film transistor liquid crystal display (TFT-LCD) monitors based on the safety margin for pathologic results. This retrospective study was approved by the institutional review board, and the requirement for informed consent was waived. A total of 105 consecutive breast cancer SM samples from 104 women who underwent BCS were included in the study. The SM were independently reviewed by two radiologists using mobile devices and by two additional radiologists using 5M TFT-LCD monitor. Each reader was asked to measure the shortest distance between the lesion and the lesion margin. The interpretation time was recorded. The sensitivity, specificity, and interobserver agreement were analyzed. In total, 19% (20/105) breast specimens had a positive surgical margin (

The purpose of this study was to identify the factors affecting hypoglycemia fear behavior and hypoglycemia anxiety among type 1 diabetes mellitus patients. A cross-sectional survey was conducted with 101 type 1 diabetes mellitus patients in South Korea via online survey. The data were analyzed by descriptive statistics, correlation and multiple regression analysis using IBM SPSS Statistics 23.0 program. The mean age of the participants was 28.31±11.68 years and 61.4% of the participants experienced hypoglycemia more than four times per month. The scores for hypoglycemia fear behavior and hypoglycemia anxiety were 29.55±6.70 (range: 13-43) and 41.11±16.39 (range: 16-80), respectively. The explanatory power of the hypoglycemia fear behavior model including three variables of age, depression, and hypoglycemia anxiety was 19.0% (F=8.75, p

The clinical significance of long-term methicillin-resistant Staphylococcus aureus (MRSA) bacteremia remains unclear. We evaluated the clinical, microbiological characteristics, and clinical outcomes of long-term MRSA bacteremia. A nested case-control study was conducted in a prospective cohort of adult patients with MRSA bacteremia at a tertiary hospital between August 2008 and December 2017. Patients with long-term MRSA bacteremia (≥ 14 days) were compared with control patients, defined as having bacteremia that resolved in less than 3 days. The following variables were documented: heteroresistance phenotype, genotypes, agr dysfunction, and the presence of 41 virulence genes in isolates. Of the total 890 patients studied, 69 patients (7.8%) exhibited long-term MRSA bacteremia and 599 (67.3%) exhibited resolving bacteremia. The most common sources of long-term bacteremia were central venous catheter–related infection (39%) and osteomyelitis (19%). Independent risk factors for long-term MRSA bacteremia included male sex (adjusted odds ratio [aOR] = 2.43), community-acquired bacteremia (aOR = 2.93), the presence of a prosthetic device (aOR = 3.40), and osteomyelitis (aOR = 7.98). Metastatic infections developed more frequently in patients with long-term bacteremia than in those with resolving bacteremia (56.5% vs. 8.0%; P

PurposeTo evaluate the role of postmastectomy radiation therapy (PMRT) in patients with node-negative breast cancer of 5cm or larger tumors undergoing mastectomyMaterials and MethodsMedical records of 274 patients from 18 institutions treated with mastectomy between January 2000 and December 2016 were retrospectively reviewed. Among these, 202 patients underwent PMRT, while 72 did not. Two hundred and forty-one patients (88.0%) received systemic chemotherapy, and 172 (62.8%) received hormonal therapy. Patients receiving PMRT were younger, more likely to have progesterone receptor-positive tumors, and received adjuvant chemotherapy more frequently compared with those without PMRT (p

Electromagnetic navigation bronchoscopy (ENB) is an emerging technique used to evaluate peripheral lung lesions. The aim of this study was to determine the diagnostic yield, safety profile, and adequacy of specimens obtained using ENB for molecular testing. This single-center, prospective pilot study recruited patients with peripheral pulmonary nodules that were not suitable for biopsy via percutaneous transthoracic needle biopsy methods. The possibility of molecular testing, including epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and programmed death ligand 1 (PD-L1), was identified with non-small cell lung cancer (NSCLC) tissue obtained using ENB. ENB-guided biopsy was performed on 30 pulmonary nodules in 30 patients. ENB-guided biopsy was successfully performed in 96.6% (29/30) of cases, but one case failed to approach the target lesion. The diagnostic accuracy of ENB-guided biopsy was 68.0% (17/25). Biopsy-related pneumothorax occurred in one patient and there was no major bleeding or deaths related to the procedure. Among 13 patients diagnosed with NSCLC, molecular testing was successfully performed in 92.3% (12/13). ENB-guided biopsy demonstrated acceptable accuracy and excellent sample adequacy, with a high possibility of achieving molecular testing and a good safety profile to evaluate peripheral pulmonary nodules, even when the percutaneous approach was difficult and/or dangerous.

We investigated the relationship between diabetes family conflict and parental conflict on problem recognition in illness self-management (PRISM) among individuals with type 1 diabetes mellitus (T1DM). We employed a descriptive research design. Participants were 243 individuals with T1DM who completed online questionnaires. Data were analyzed with descriptive statistics, correlations, and multiple regression analyses. Results revealed that barriers were felt in all areas (understanding and organizing care, regimen pain and bother, healthcare team interaction, family interaction, and peer interaction), especially peer interaction. The significant influencing factors in the regression model for the total PRISM score of individuals with T1DM were conflict behavior toward mothers (t = 4.44, p &lt, 0.001), diabetes family conflict (t = 5.77, p &lt, 0.001), conflict behavior toward fathers (t = 2.58, p = 0.011), women (t = 2.67, p = 0.008), non-religious (t = −2.33, p = 0.020), and diabetic complications (t = 2.17, p = 0.031). The explanatory power of the constructed regression model for PRISM was 42.0% (F = 30.12, p &lt, 0.001). To promote self-management among individuals with T1DM, the development of interventions that promote improved peer interactions, a family-centered approach, and a program that can minimize conflicts between families and parents are required.

This study investigated the association between the quality of life (QOL) and type 1 diabetes mellitus (DM), a lifelong disease that requires constant management. A complex set of factors influence the QOL of people with type 1 DM, and understanding these factors requires further research. This research is a cross-sectional descriptive study. A survey on related variables such as acceptance of disease and efficacy for self-management of diabetes, was conducted among 111 participants with type 1 DM. The collected data were analyzed using PASW Statistics program, and factors influencing participants’ QOL were identified through hierarchical multiple regression. The study followed the Guidelines of Systematic Reporting of Examination in the STROBE checklist. The results showed that four variables exerted a significant effect on QOL (blood glucose level at hypoglycemia and complications in Model 1, efficacy for self-management of diabetes and acceptance and action in Model 2), and all the variables explained a majority of the variance in QOL. The results indicate that management of severe hypoglycemia and prevention of complications is crucial. Interventions should be developed to enhance coping abilities to improve efficacy for self-management for those with diabetes and promote their acceptance of the disease.

Objective As the heritability of hyperuricaemia remains largely unexplained, we analysed the association between parental and offspring hyperuricaemia at the phenotype level. Methods This cross-sectional study included data on 2373 offspring and both-parent pairs from the seventh Korean National Health and Nutrition Examination Survey. Logistic regression and generalised estimating equation analysis were used to evaluate the association between offspring and parental hyperuricaemia adjusting for metabolic risk factors and alcohol intake. Results Both maternal and paternal hyperuricaemia were associated with offspring hyperuricaemia among teenagers, but from the age of 20 years, a strong association was observed between offspring and paternal, rather than, maternal hyperuricaemia, and this could not be explained by metabolic risk factors such as obesity. However, there was a positive interaction between offspring alcohol intake and parental hyperuricaemia, and there was a stronger association between terciles of offspring alcohol intake and hyperuricaemia in the presence of parental hyperuricaemia: T1 (reference), T2 odds ratio (OR) 1.1 (0.3–4.6), and T3 OR 3.3 (1.4–7.9) (P for trend .017) vs. T1 (reference), T2 OR 0.7 (0.3–1.9), and T3 OR 1.1 (0.6–2.2) (P for trend .974). Conclusion These results suggest a gene–environment interaction, especially with respect to alcohol intake for hyperuricaemia in Korean adults.

Background To map anatomic patterns of para-aortic lymph node (PALN) recurrence in cervical cancer patients and validate currently available guidelines on PA clinical target volumes (CTV). Methods Cervical cancer patients who developed PALN recurrence were included. The PALNs were classified as left-lateral para-aortic (LPA), aorto-caval (AC), and right para-caval (RPC). Four PA CTVs were contoured for each patient to validate PALN coverage. CTVRTOG was contoured based on the Radiation Therapy Oncology Group guideline. CTVK was contoured as proposed by Keenan et al. CTVM was contoured by expanding symmetrical margins around the aorta and inferior vena cava of 7 mm up to the T12–L1 interspace. CTVnew was created by modifying CTVRTOG to obtain better coverage. Results We identified 92 PALNs in 35 cervical cancer patients. 46.8% of the PALNs were at LPA, 38.0% were at AC, and 15.2% were at RPC areas. CTVRTOG, CTVK, and CTVM covered 87.0%, 88.0%, and 62.0% of all PALNs, respectively. PALN recurrence above the left renal vein was associated with PALN involvement at diagnosis (p = 0.043). Extending upper border to the superior mesenteric artery allowed the CTVnew to cover 96.7% of all PALNs and all nodes in 91.4% of patients. Conclusion CTVRTOG and CTVK encompassed most PALN recurrences. For high-risk patients, such as those having PALN involvement at diagnosis, extending the superior border of CTV from the left renal vein to superior mesenteric artery could be considered.

Background/aim To present the variations in the target delineation and the planning results of intensity-modulated radiation therapy (IMRT) for breast cancers. Patients and methods We requested the target volumes and organs at risk delineation for two cases of left breast cancers, and evaluated the IMRT plans including the supraclavicular and internal mammary node irradiation. Results Twenty-one institutions participated in this study. Differences in the planning target volume among institutions reached up to three-times for breast-conserving surgery (BCS) case and five-times for mastectomy case. Mean heart doses ranged from 3.3 to 24.1 Gy for BCS case and from 5.0 to 26.5 Gy for mastectomy case. Ipsilateral lung volumes receiving more than 20 Gy ranged from 4.7 to 57.4% for BCS case and from 16.4 to 55.5% for mastectomy case. Conclusion There were large variations in the target delineation and planning results of IMRT for breast cancers among institutions. Considering the increased use of breast IMRT, more standardized protocols are needed.

The purposes of this study were to investigate the trajectory groups of depressive symptoms and anxiety in women during pregnancy and to identify the factors associated with those groups. Participants were recruited from the outpatient clinic of a women’s health hospital in Seoul, Korea. Pregnant women (n = 136) completed a survey questionnaire that included questions on depressive symptoms, anxiety, and pregnancy stress, additionally, their saliva was tested for cortisol hormone levels three times during their pregnancies. The group-based trajectory modeling approach was used to identify latent trajectory groups. Ordinal logistic regressions were used to explore the association of latent trajectory groups with sociodemographic factors and pregnancy stress. Three trajectory groups of depressive symptoms were identified: low-stable (70%), moderate-stable (25%), and increased (5%). Four trajectory groups of anxiety were identified: very low-stable (10%), low-stable (67%), moderate-stable (18%), and high-stable (5%). The only factor associated with both the depressive symptoms and anxiety trajectory groups was pregnancy stress (p &lt, 0.001). Most participants showed stable emotional status, however, some participants experienced higher levels of depressive symptoms and anxiety related to higher pregnancy stress. These pregnant women may need additional care from healthcare providers to promote their wellbeing during pregnancy.

Background Electromagnetic navigation bronchoscopy (ENB) is a useful method to obtain tissue for peripheral lung nodules. We aimed to understand the diagnostic yield and safety profile in high‐risk pulmonary nodules that cannot be accessed by percutaneous transthoracic needle biopsy. Methods In this single‐center retrospective study, we reviewed patients who underwent ENB for high‐risk pulmonary nodules. All procedures were performed under moderate sedation using intravenous midazolam and fentanyl. Results A total of 100 pulmonary nodules in 90 patients were subjected to ENB between October 2018 and May 2020. The median age of the study population was 66 (59–73). The mean diameter of the lung nodules was 27.9 mm. The diagnostic yield of ENB‐guided biopsy was 53.0%. Although the nodule size (odds ratio: 1.055, p = 0.007) and positive bronchus sign (odds ratio: 2.918, p = 0.020) were associated with the diagnostic yield during univariate analysis, nodule size was the only independent variable on the multivariable analysis. Interestingly, the diagnostic yield showed an upward trend after 60 cases, from 45%–65%. Procedure‐related complications were reported in 16 cases; among these, pneumothorax occurred in three cases, and four cases experienced moderate bleeding. No instance of major bleeding or death was linked to ENB‐guided biopsy. Conclusion ENB‐guided biopsy for high‐risk pulmonary nodules demonstrated an acceptable diagnostic yield and good safety profile. Moreover, the diagnostic yield was associated with nodule size and procedure experience., In this single‐center retrospective study, we reviewed a total of 100 pulmonary nodules in 90 patients who underwent ENB for high‐risk pulmonary nodules under moderate sedation. The diagnostic yield of ENB‐guided biopsy was 53.0% and showed an upward trend after 60 cases, from 45%–65%. The diagnostic yield was associated with nodule size and the operator's experience with the procedure. Procedure‐related complications were reported in 16 cases without major bleeding events or death. ENB can be used for high‐risk patients because of an acceptable diagnostic yield and a good safety profile.

While chest CT provides important clue for diagnosis of miliary tuberculosis (TB), patients are occasionally missed on initial CT, which might delay the diagnosis. This study was to evaluate the clinical and radiological characteristics of radiologically missed miliary TB. Total 117 adult patients with microbiologically confirmed miliary TB in an intermediate TB-burden country were included. ‘Missed miliary TB’ were defined as the case in which miliary TB was not mentioned as a differential diagnosis in the initial CT reading. Clinical characteristics and radiologic findings including the predominant nodule size, demarcation of miliary nodules and disease extent on CT were retrospectively evaluated. Findings were compared between the missed and non-missed miliary TB groups. Multivariable analyses were performed to determine independent risk factors of missed miliary TB. Of 117 patients with miliary TB, 13 (11.1%) were classified as missed miliary TB; these patients were significantly older than those with non-missed miliary TB (median age, 71 vs 57 years, P = .024). There was a significant diagnostic delay in the missed miliary TB group (P

Background Afatinib is approved globally for EGFR-TKI treatment-naïve patients with EGFR mutation-positive non-small cell lung cancer (NSCLC). In this Korean expanded access program, we evaluated its ‘real-world’ safety and efficacy. Methods EGFR-TKI treatment-naïve patients with EGFR mutation-positive NSCLC received afatinib 40 mg/day until disease progression or other withdrawal criteria. Dose reductions were permitted for adverse events (AEs). The primary endpoint was the number of patients with AEs (CTCAE version 3.0). Other endpoints included progression-free survival (PFS), overall response rate (ORR), duration of response (DOR), and changes in investigator-assessed cancer-related symptoms. Results Eighty-eight patients received afatinib, including 27 (31%) with brain metastases and 16 (18%) with uncommon EGFR mutations. Median PFS was 17.0 months (95% confidence interval [CI] 12.9–23.3 months). Grade 3 treatment-related AEs (TRAEs) were reported in 51 (58%) patients; the most common were diarrhea (22%) and rash/acne (20%). No grade > 3 TRAEs were reported. AEs leading to dose reduction occurred in 49 (56%) patients. Treatment discontinuation due to TRAEs occurred in 4 (5%) patients. ORR was 81% overall, 89% in patients with brain metastases, and 55% in patients with uncommon mutations (excluding T790M/exon 20 insertions). Median DOR was 15.1 months (95% CI 12.4–21.4 months). Cancer-related symptoms were improved/unchanged/worsened in 34–66%/36–66%/0–3% of patients over the first year. Conclusions No unexpected safety signals for afatinib were observed. AEs were manageable; the treatment discontinuation rate was low. Afatinib showed encouraging efficacy in a broad patient population including those with brain metastases or tumors harboring uncommon EGFR mutations. Trials registration ClinicalTrials.gov NCT01931306; 29/08/2013.

IntroductionWe assessed the applicability of next-generation sequencing (NGS)-basedIGH/IGKclonality testing and analyzed the repertoire of immunoglobulin heavy chain (IGH) or immunoglobulin kappa light chain (IGK) gene usage in Korean patients with multiple myeloma (MM) for the first time.MethodsFifty-nine bone marrow samples from 57 Korean patients with MM were analyzed, and NGS-based clonality testing that targeted theIGHandIGKgenes was performed usingIGHFR1 andIGKprimer sets.ResultsClonalIGHandIGKrearrangements were observed in 74.2% and 67.7% of samples from Korean patients with kappa-restricted MM, respectively (90.3% had one or both), and in 60.7% and 95.5% of samples from those with lambda-restricted MM, respectively (85.7% had one or both). In total, 88.1% of samples from Koreans with MM had clonalIGHand/orIGKrearrangement. Clonal rearrangement was not significantly associated with the bone marrow plasma cells as a proportion of all BM lymphoid cells.IGHV3-9(11.63%) andIGHV4-31(9.30%) were the most frequently reportedIGHVgenes and were more common in Koreans with MM than in Western counterparts.IGHD3-10andIGHD3-3(13.95% each) were the most frequent IGHD genes;IGHD3-3was more common in Koreans with MM. NoIGKrearrangement was particularly prevalent, but singleIGKV-Jrearrangements were less common in Koreans with kappa-restricted MM than in Western counterparts.IGKV4-1was less frequent in Koreans regardless of light chain type. Otherwise, the usages of theIGHV, D, and J genes and of theIGKgene were like those observed in previous Western studies.ConclusionNGS-basedIGH/IGKclonality testing ought to be applicable to most Koreans with MM. The overrepresentation ofIGHV3-9,IGHV4-31, andIGHD3-3along with the underrepresentation ofIGKV4-1and the differences inIGKgene rearrangement types suggest the existence of ethnicity-specific variations in this disease.

Owing to increased awareness of the importance of mammogram and advances in surgical technology, survival rate of patients with primary breast cancer has dramatically increased. Despite all these advances in breast cancer treatment, there are no currently available treatments for this disease once it metastasizes to distant organs including bones, lungs, brain, and liver. This is mainly attributed to the complexity of metastatic process. Recent advances in technology enabled cancer biologists to dissect each step of the metastatic process, and this led to discovery of major players and molecules in this process. In this section, we will discuss recent discovery and advances in the field of breast cancer metastasis research.

Smallpox, a disease caused by the variola virus, is one of the most dangerous diseases and had killed numerous people before it was eradicated in 1980. However, smallpox has emerged as the most threatening bio-terrorism agent; as the first- and second-generation smallpox vaccines have been controversial and have caused severe adverse reactions, new demands for safe smallpox vaccines have been raised and some attenuated smallpox vaccines have been developed. We have developed a cell culture-based highly attenuated third-generation smallpox vaccine candidate KVAC103 strain by 103 serial passages of the Lancy-Vaxina strain derived from the Lister in Vero cells. Several clones were selected, taking into consideration their shape, size, and growth rate in mammalian cells. The clones were then inoculated intracerebrally in suckling mice to test for neurovirulence by observing survival. Protective immune responses in adult mice were examined by measuring the levels of neutralization antibodies and IFN-γ expression. Among several clones, clone 7 was considered the best alternative candidate because there was no mortality in suckling mice against a lethal challenge. In addition, enhanced neutralizing antibodies and T-cell mediated IFN-γ production were observed in clone 7-immunized mice. Clone 7 was named “KVAC103” and was used for the skin toxicity test and full-genome analysis. KVAC103-inoculated rabbits showed reduced skin lesions compared to those inoculated with the Lister strain, Lancy-Vaxina. A whole genome analysis of KVAC103 revealed two major deleted regions that might contribute to the reduced virulence of KVAC103 compared to the Lister strain. Phylogenetic inference supported the close relationship with the Lister strain. Collectively, our data demonstrate that KVAC103 holds promise for use as a third-generation smallpox vaccine strain due to its enhanced safety and efficacy.

Background Adverse drug events (ADEs) resulting from medication error are some of the most common causes of iatrogenic injuries in hospitals. With the appropriate use of medication, ADEs can be prevented and ameliorated. Efforts to reduce medication errors and prevent ADEs have been made by implementing a medication decision support system (MDSS) in electronic health records (EHRs). However, physicians tend to override most MDSS alerts. Objective In order to improve MDSS functionality, we must understand what factors users consider essential for the successful implementation of an MDSS into their clinical setting. This study followed the implementation process for an MDSS within a comprehensive EHR system and analyzed the relevant barriers and facilitators. Methods A mixed research methodology was adopted. Data from a structured survey and 15 in-depth interviews were integrated. Structural equation modeling was conducted for quantitative analysis of factors related to user adoption of MDSS. Qualitative analysis based on semistructured interviews with physicians was conducted to collect various opinions on MDSS implementation. Results Quantitative analysis revealed that physicians’ expectations regarding ease of use and performance improvement are crucial. Qualitative analysis identified four significant barriers to MDSS implementation: alert fatigue, lack of accuracy, poor user interface design, and lack of customizability. Conclusions This study revealed barriers and facilitators to the implementation of MDSS. The findings can be applied to upgrade MDSS in the future.

Recently, biological markers of maternal prenatal stress, hair cortisol, along with saliva, blood, and urine cortisol, have received attention. However, it is necessary to validate measuring hair cortisol concentrations (HCC) as a biomarker of perceived stress among healthy and high-risk pregnant women. This study aimed to confirm the correlation between HCC and the perceived stress of pregnant women over 18 years of age. In this systematic review, we used various search engines to extract relevant articles using specific keywords related to pregnancy, hair cortisol, and psychological stress. Four out of 3639 studies met the inclusion criteria. We conducted a quality assessment with the help of three independent reviewers using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement. The correlation between HCC and perceived stress was confirmed in one study. There was only one study on hair washing, shampoo, conditioner, and hair structure that could affect hair samples. In four studies, hair samples differed in length, methods of storage, and laboratory analysis. The review was limited to confirming the relationship between HCC and perceived stress in pregnant women based on the current evidence. Studies on hair cortisol need regulated and standardized methods for collection, storage, and analysis of hair samples.

Lung cancer screening with low-dose computed tomography reduced mortality in selected high risk patients. However, the use of chest radiography for lung cancer screening in Asian populations is still controversial. We investigated the effectiveness of chest radiographic surveillance using a nationwide health service data in South Korea.Data from the Korean National Health Insurance Service examinee cohort of 2004 to 2013 were examined, and 63,228 patients with lung cancer were identified, 38,494 (57%) of whom underwent chest radiography screening. The others did not undergo lung cancer screening and were considered as a control group. Clinical data including age, smoking, screening intervals, lung cancer stages, treatments, and survival were collected. Survival gain from surveillance after adjustment for lead-time bias based on the sojourn time was calculated. Cox-proportional hazard analyses were performed to evaluate the effectiveness of screening and to determine the appropriate screening interval for chest radiography surveillance.Early lung cancer was found in 38% of patients receiving chest radiography versus 26% of those without surveillance. A patient age of more than 65 years (hazard ratio [HR], 1.53; 95% confidence limits [CL], 1.50-1.56), male (HR, 1.66; 95% CL, 1.62-1.70), and high lung cancer stages at the time of diagnosis were independent factors associated with mortality (each, P 0.001). Chest radiography surveillance was a factor for decreasing mortality in female (HR, 0.81; 95% CL, 0.77-0.84, P 0.001), with mortality reduction of 10% at the 3- and 5-year survival time-points. In female patients, chest radiography surveillance at intervals of less than 3 years was an independent predictor of improved survival.Surveillance chest radiography increased survival in a female screened population in South Korea. Chest radiography intervals of less than 3 years may help to detect lung cancer in female patients.

Purpose To determine the necessity of postmastectomy radiotherapy (PMRT) and which regions would be at risk for recurrence, we evaluated local and regional recurrence in breast cancer patients with 1–3 positive nodes and a tumor size of

Background: The sensitivity of galactomannan (GM) assay is suboptimal for detecting invasive pulmonary aspergillosis (IPA) in serum samples. However, the clinical characteristics, radiologic findings, and outcomes in patients with GM-negative IPA have not been fully elucidated. Methods: Over a 7-year period, adult patients with proven or probable IPA by the EORTC/MSG definition were retrospectively enrolled. Patients with negative GM results and positive Aspergillus spp. cultures from sputum or bronchoalveolar lavage were classified into GM-negative IPA group. GM-positive and culture-negative IPA cases were selected at a 1:2 ratio. Results: Thirty-four patients with GM-negative IPA were compared to 68 randomly selected patients from 158 patients with GM-positive and culture-negative IPA. Patients with diabetes mellitus, chronic kidney disease, and steroid use were more common but those with hematologic malignancy, prior receipt of mold-active antifungal drugs, and neutropenia were less common in GM-negative IPA than in GM-positive IPA. Regarding radiologic findings, angioinvasive aspergillosis was less common in GM-negative IPA than in GM-positive IPA. The median number of days from diagnosis to appropriate antifungal therapy was higher in GM-negative IPA than in GM-positive IPA. Multivariate analysis indicated that neutropenia (adjusted odds ratio [aOR], 0.10) and prior receipt of mold-active antifungal drugs (aOR, 0.12) were inversely associated with GM-negative IPA. The 30-day and 90-day mortality were similar between the two groups. Conclusion: Neutropenia and prior receipt of mold-active antifungal drugs before GM assay were independently associated with GM positivity among patients with proven/probable IPA. Angioinvasive aspergillosis was less common in GM-negative IPA than in GM-positive IPA. Keywords: Galactomannan, Invasive pulmonary aspergillosis, Neutropenia

Background : Nephrotic syndrome (NS) is the most common glomerulopathy in children. Acute kidney injury (AKI) is a common complication of NS, caused by severe intravascular volume depletion, acute tubular necrosis, interstitial nephritis, or progression of NS. However, the incidence and risk factors of childhood-onset NS in Korea are unclear. Therefore, we studied the incidence, causes, and risk factors of AKI in hospitalized Korean patients with childhood-onset NS. Methods : We conducted a retrospective review of patients with childhood-onset NS who were admitted to our center from January 2015 to July 2017. Patients with decreased renal function or hereditary/secondary NS, as well as those admitted for management of other conditions unrelated to NS, were excluded. Results : During the study period, 65 patients with idiopathic, childhood-onset NS were hospitalized 90 times for management of NS or its complications. Of these 90 cases, 29 met the Kidney Disease Improving Global Outcomes criteria for AKI (32.2%). They developed AKI in association with infection (n = 12), NS aggravation (n = 11), dehydration (n = 3), and intravenous methylprednisolone administration (n = 3). Age ≥ 9 years at admission and combined use of cyclosporine and renin-angiotensin system inhibitors were risk factors for AKI. Conclusion : AKI occurred in one-third of the total hospitalizations related to childhood-onset NS, owing to infection, aggravation of NS, dehydration, and possibly high-dose methylprednisolone treatment. Age at admission and use of nephrotoxic agents were associated with AKI. As the AKI incidence is high, AKI should be considered during management of high-risk patients.

Dementia, characterized by a progressive cognitive decline and a cumulative inability to behave independently, is highly associated with other diseases. Various cardiovascular disorders, such as coronary artery disease and atrial fibrillation, are well-known risk factors for dementia. Currently, increasing evidence suggests that sex factors may play an important role in the pathogenesis of diseases, including cardiovascular disease and dementia. Recent studies show that nearly two-thirds of patients diagnosed with Alzheimer’s disease are women; however, the incidence difference between men and women remains vague. Therefore, studies are needed to investigate sex-specific differences, which can help understand the pathophysiology of dementia and identify potential therapeutic targets for both sexes. In the present review, we summarize sex differences in the prevalence and incidence of dementia by subtypes. This review also describes sex differences in the risk factors of dementia and examines the impact of risk factors on the incidence of dementia in both sexes.

CT characteristics such as peripheral tumor location with vascular convergence, the presence of a pleural tag, and air bronchogram of lung lesions, at the time of rebiopsy, were significantly associated with positivity for the T790M mutation in patients with non–small cell lung cancer after first-line epidermal growth factor receptor–tyrosine kinase inhibitor therapy failure.

Idiopathic pulmonary fibrosis (IPF) is associated with an increased incidence of lung cancer, but patients with IPF often have poor pulmonary function and are vulnerable to pneumothorax and so using an invasive procedure to diagnose a single nodule detected on chest CT risks a critical adverse outcome. 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) is recognized to be useful for differentiating between benign and malignant solitary pulmonary nodules (SPN) in patients without IPF, but its diagnostic accuracy has not been investigated in patients with IPF. In this study, therefore, we investigated whether 18F-FDG PET/CT is useful for the differential diagnosis of SPNs in patients with IPF. From the IPF patient cohort of our institution, we retrospectively reviewed 55 patients (54 men, 1 woman; age 67.8 ± 7.6 years) with an SPN sized 8–30 mm (mean 18.5 ± 5.7 mm) who underwent chest CT followed by 18F-FDG PET/CT between April 2004 and March 2016. The 18F-FDG uptake of the SPN was analyzed visually and semiquantitatively, and these determinations were compared with the final diagnosis obtained by pathology (n = 52) or imaging follow-up (n = 3). The final diagnoses showed that 41 (75%) of the SPNs were malignant (21 squamous cell carcinomas, 9 adenocarcinomas, 5 small-cell carcinomas, 4 mixed-type carcinomas, 1 large-cell neuroendocrine carcinoma, and 1 sarcoid carcinoma) and 14 (25%) were benign. The determination of malignant SPNs by visual analysis of the PET/CT images had a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 98, 86, 95, and 92%, respectively. The semiquantitative analysis using a maximum standardized uptake value of 2.0 as the cut-off had a sensitivity, specificity, PPV, and NPV of 95, 93, 98, and 87%, respectively. 18F-FDG PET/CT is useful for differentiating benign and malignant SPNs in patients with IPF, as it is for patients without IPF.

Prolactin regulatory element-binding (PREB) protein is a transcription factor that regulates prolactin (PRL) gene expression. PRL, also known as luteotropic hormone or luteotropin, is well known for its role in producing milk. However, the role of PREB, in terms of hepatic glucose metabolism, is not well elucidated. Here, we observed expression of Preb in the mouse liver, in connection with glucose homeostasis. Morevoer, Preb was downregulated in db/db, ob/ob and high-fat diet-induced obese (DIO) mice, concurrent with upregulation of the liver genes glucose-6-phosphatase (G6pc) and phosphoenolpyruvate carboxykinase-1 (Pck). Administration of adenovirus-Preb (Ad-Preb) to db/db, ob/ob, and DIO mice diminished glucose, insulin, and pyruvate tolerance, which analogously, were impaired in normal (C57BL/6) mice knocked down for Preb, via infection with Ad-shPreb (anti-Preb RNA), indicating Preb to be a negative regulator of liver gluconeogenic genes. We further demonstrate that Preb negatively influences gluconeogenic gene expression, by directly binding to their promoters at a prolactin core-binding element (PCBE). A better understanding of Preb gene expression, during the pathogenesis of hepatic insulin resistance, could ultimately provide new avenues for therapies for metabolic syndrome, obesity, and type-2 diabetes mellitus, disorders whose worldwide incidences are increasing drastically.

Mosquito-borne tropical dengue disease is a major global epidemic affecting hundreds of millions of people. As a precaution, it would be ideal to develop a highly efficient tetravalent vaccine that protects against all serotypes of dengue viruses. In this study, envelope protein domain III (EDIII) of dengue virus was employed as a target antigen. A single-chain tetravalent type of EDIII (tEDIII) was generated by utilizing a linker peptide and transformed into rice (Oryza sativa). Integration and mRNA transcripts of the tEDIII gene were confirmed by genomic DNA polymerase chain reaction (PCR) and Northern blot analyses, respectively. The expression of wild-type tEDIII (wtEDIII) protein was confirmed by Western blot analysis and was determined to improve the synthesis of the tEDIII (stEDIII) construct based on codon optimization and ER targeting. The yield of stEDIII protein was sevenfold higher than secreted wtEDIII protein, reaching a maximum of 357 µg per gram dry weight. These results suggest that a simple tetravalent EDIII dengue antigen can be produced in rice, raising the possibility that edible plant cells can be vaccinated by mucosal application for protection against dengue infection.

Background/Aims The annual risk of transformation of non-hypervascular magnetic resonance (MR) hepatobiliary phase imaging (HBPI) hypointense nodules into hypervascular hepatocellular carcinomas (HCCs) was evaluated. Methods Cirrhotic patients with non-hypervascular HBPI hypointense nodules were retrospectively analyzed if they were diagnosed as HCC and MR followed up longer than 1 year during the period from January 2010 to October 2016 with regular intervals of 3 to 6 months. Risk factors for transformation into hypervascular HCCs were analyzed using the Cox proportional hazard model. Results Among the 103 non-hypervascular HBPI hypointense nodules meeting the inclusion criteria, transformation into hypervascular HCCs occurred in 44 tumors (42.7%). The median follow-up period was 24 months. Multivariate analysis revealed that hyperintensity on T2-weighted images (T2WI) and diffusion-weighted images (DWI) were the two independent predictors of transformation into hypervascular HCCs (p=0.036 and p=0.041, respectively). Most tumors with hyperintensity on T2WI or DWI on the initial or follow-up MR were transformed into hypervascular HCCs within the first year. Among the 22 nodules (21.3%) showing a new change in dynamic phases during follow-up, 14 nodules (13.6%) showed malignant transformations. Conclusions The transformation rates of HBPI hypointense nodules into hypervascular HCCs could be predicted according to the initial or serial MRI findings.

Background Non-invasive anatomical and physiological evaluations of coronary artery disease (CAD) may be obtained with static single-scan stress perfusion cardiac computed tomography (SSPCT). Purpose To determine the diagnostic performance of static SSPCT for identifying hemodynamically significant CAD. Material and Methods This prospective study included 29 patients with suspected or known CAD who underwent static SSPCT, cardiovascular magnetic resonance myocardial perfusion imaging (CMR-MPI), and invasive coronary angiography (ICA). CT was performed as follows: (i) coronary calcium scan; (ii) static SSPCT for both coronary artery (coronary CT angiography [CCTA]) and myocardial perfusion (perfusion CT [PCT]) during adenosine infusion; (iii) late-phase scan. The diagnostic performance of CCTA alone, PCT alone, and SSPCT for the detection of a hemodynamically significant CAD (a perfusion defect in a vascular territory subtended by a coronary vessel with ≥ 50% stenosis) was compared with that of combined ICA/CMR-MPI representing the standard of reference. Results Twenty-three (79%) patients and 47 (54%) vascular territories manifested ischemia-causing coronary stenoses by combined ICA/CMR-MPI. The per-vessel sensitivity, specificity, positive and negative predictive values, and area under the receiver operating characteristic curve (AUC) of the SSPCT were 92%, 88%, 90%, 90%, and 0.90, respectively, compared to those of the combined ICA/CMR-MPI. These values for the CCTA alone were 96%, 63%, 75%, 93%, and 0.79, respectively; and the values for the PCT alone were 94%, 83%, 86%, 92%, and 0.88, respectively. The AUC of SSPCT was significantly ( P = 0.013) higher than that of the CCTA alone. Conclusion Static SSPCT may facilitate detection of hemodynamically significant CAD.

Pemphigus vulgaris is an autoimmune bullous disorder characterized by the production of autoantibodies against the intercellular space of the epithelium. It has rarely been reported in association with inflammatory bowel disease. Ulcerative colitis is one of the forms of inflammatory bowel disease. A 62-year-old woman who had been treated for ulcerative colitis for 16 years developed pruritic bullae on the skin of her face and body. Histological findings and direct immunofluorescence examination of the skin showed pemphigus vulgaris. She was treated with systemic steroids, mesalazine, and azathioprine. Her cutaneous lesions have remained in remission and her ulcerative colitis has remained well-controlled. The relationship between pemphigus vulgaris and ulcerative colitis is unclear. An autoimmune response has been suspected in the pathogenesis of ulcerative colitis. Pemphigus vulgaris is also associated with an autoimmune mechanism. To our knowledge, this is the first case of ulcerative colitis associated with pemphigus vulgaris reported in Korea. The association may be causal.

Little is known about the pathogenesis or molecular profiles of idiopathic pulmonary fibrosis-associated lung cancer (IPF-LC). This study was performed to investigate the genomic profiles of IPF-LC and to explore the possibility of defining potential therapeutic targets in IPF-LC. We assessed genomic profiles of IPF-LC by using targeted exome sequencing (OncoPanel version 2) in 35 matched tumour/normal pairs surgically resected between 2004 and 2014. Germline and somatic variant calling was performed with GATK HaplotypeCaller and MuTect with GATK SomaticIndelocator, respectively. Copy number analysis was conducted with CNVkit, with focal events determined by Genomic Identification of Significant Targets in Cancer 2.0, and pathway analysis (KEGG) with DAVID. Germline mutations in TERT (rs2736100, n = 33) and CDKN1A (rs2395655, n = 27) associated with idiopathic pulmonary fibrosis risk were detected in most samples. A total of 410 somatic mutations were identified, with an average of 11.7 per tumour, including 69 synonymous, 177 missense, 17 nonsense, 1 nonstop and 11 splice-site mutations, and 135 small coding indels. Spectra of the somatic mutations revealed predominant C > T transitions despite an extensive smoking history in most patients, suggesting a potential association between APOBEC-related mutagenesis and the development of IPF-LC. TP53 (22/35, 62.9%) and BRAF (6/35, 17.1%) were found to be significantly mutated in IPF-LC. Recurrent focal amplifications in three chromosomal loci (3q26.33, 7q31.2, and 12q14.3) and 9p21.3 deletion were identified, and genes associated with the JAK-STAT signalling pathway were significantly amplified in IPF-LC (P = 0.012). This study demonstrates that IPF-LC is genetically characterized by the presence of somatic mutations reflecting a variety of environmental exposures on the background of specific germline mutations, and is associated with potentially targetable alterations such as BRAF mutations. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

We investigated the usefulness of abbreviated breast MRI (AB-MRI), including fat-suppressed T2-weighted imaging, pre- and postcontrast image acquisition, and subtracted maximum-intensity projection imaging, for the screening of women with a history of breast cancer surgery. Between October 2014 and March 2016, a total of 799 AB-MRI examinations were performed for 725 women with a history of breast cancer surgery. The image acquisition time was 8.5 min. Screening mammography, ultrasound, and AB-MRI were generally performed around the same time. The cancer detection rate, positive predictive values for recall and biopsy, sensitivity and specificity of screening MRI, and rate of malignancy belonging to each breast imaging reporting and data system (BI-RADS) category were assessed. AB-MRI detected 12 malignancies in 12 women (15.0 cancers per 1000 cases). Seven of these 12 malignancies were initially invisible on ultrasound and mammography, although subsequent targeted ultrasound revealed lesions corresponding to the MRI-detected lesions. The positive predictive values for recall and biopsy and sensitivity and specificity values for screening MRI were 12.4, 61.5, 100, and 89.2%, respectively. The rates of malignancies belonging to categories 1, 2, 3, and 4 of the BI-RADS were 0, 0, 4.8, and 57.1%, respectively. The diagnostic performance of screening AB-MRI for women with a history of breast cancer surgery is acceptable, with the advantages of short examination and interpretation times and low costs. Thus, it could be used as a main screening modality that may replace conventional imaging in breast cancer survivors.

Purpose To evaluate the feasibility of simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) for preoperative concurrent chemoradiotherapy (PCRT) in locally advanced rectal cancer (LARC), by comparing with 3-dimensional conformal radiotherapy (3D-CRT). Materials and methods Patients who were treated with PCRT for LARC from 2015 January to 2016 December were retrospectively enrolled. Total doses of 45 Gy to 50.4 Gy with 3D-CRT or SIB-IMRT were administered concomitantly with 5-fluorouracil plus leucovorin or capecitabine. Surgery was performed 8 weeks after PCRT. Between PCRT and surgery, one cycle of additional chemotherapy was administered. Pathologic tumor responses were compared between SIB-IMRT and 3D-CRT groups. Acute gastrointestinal, genitourinary, hematologic, and skin toxicities were compared between the two groups based on the RTOG toxicity criteria. Results SIB-IMRT was used in 53 patients, and 3D-CRT in 41 patients. After PCRT, no significant differences were noted in tumor responses, pathologic complete response (9% vs. 7%; p = 1.000), pathologic tumor regression Grade 3 or higher (85% vs. 71%; p = 0.096), and R0 resection (87% vs. 85%; p = 0.843). Grade 2 genitourinary toxicities were significantly lesser in the SIB-IMRT group (8% vs. 24%; p = 0.023), but gastrointestinal toxicities were not different across the two groups. Conclusion SIB-IMRT showed lower GU toxicity and similar tumor responses when compared with 3D-CRT in PCRT for LARC.

The feasibility of a safe and cost-effective oral dengue vaccine approach was investigated. Consensus domain III of the dengue virus (DENV) serotypes 1–4 envelope glycoprotein was fused with cholera toxin B subunit (CTB–cEDIII) and cloned into TMV-based 3′ pro-module for high level expression. The construct was co-infiltrated with TMV-based 5′ pro-module and Integrase module into Nicotiana benthamiana leaves using vacuum agroinfiltration. CTB–cEDIII fusion protein directed to endoplasmic reticulum by C-terminal SEKEDL sequence was expressed at up to 8.4% of total soluble protein at 5 days-post infiltration (dpi). After oral immunization of mice with the transiently expressed plant-derived CTB–cEDIII, high titers of serum IgG and sIgA against both cEDIII and CTB were observed, peaking at week four. Sera from immunized mice reacted with each of the four DENV serotype-specific envelope proteins domain III. These results show that (i) the TMV-based pro-vector system is suitable for high-level expression of antigen in plant cells and (ii) the CTB fusion with cEDIII could be exploited as an oral vaccine candidate for induction of both systemic and mucosal immune responses to DENV.

Mammography detects calcium deposits sensitively, but the specificity for differentiating malignancy from benign calcifications is low. Thus, we investigated whether adjunctive breast-specific gamma imaging (BSGI) has incremental value for detecting cancer in women with suspicious calcifications detected by mammography, and compared BSGI with adjunctive ultrasonography (US). The medical records of women without a personal history of breast cancer who underwent mammography for breast evaluation from 2009 to 2014 were reviewed retrospectively. Patients who had calcifications detected by mammography, with a result of Breast Imaging Reporting and Data System (BI-RADS) categories 3–5, underwent adjunctive US and BSGI and were included in this study. A total of 302 breast lesions in 266 women (mean age ± standard deviation 49 ± 9 years) were selected for this study. For detecting breast cancer using mammography plus BSGI, the sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating curve with 95% confidence intervals were 94% (91–96), 90% (86–93), 91% (87–94), 94% (90–96), and 0.92 (0.89–0.95), respectively. For mammography plus US, the respective values were 97% (94–98), 51% (46–57), 68% (63–73), 94% (90–96), and 0.74 (0.70–0.78). Adjunctive BSGI had higher specificity than adjunctive US without loss of sensitivity. This finding suggests that adjunctive BSGI may be a useful complementary initial imaging method to improve the detection of breast cancer in women who have calcifications with suspicious morphology at mammography.

This study aimed to determine the association between statins and the prevention of dementia according to sex differences in elderly patients with ischemic heart disease (IHD). We performed a nationwide retrospective cohort study using the Korean Health Insurance Review and Assessment Service database (2007&ndash, 2015). Among the 264,036 eligible patients aged &ge, 65 years with IHD, statin users were compared with non&ndash, users by propensity score matching at a 1:1 ratio (71,587 in each group). The primary outcome was dementia risk by estimating hazard ratios (HRs) and 95% confidence intervals (CIs). Differential risks of dementia were assessed by sex in the subgroups of statin types, exposure duration, and patient age, implying that sex is an influential factor for the link between statin use and dementia incidence. Among seven commonly prescribed statins, rosuvastatin was associated with the greatest preventive effect on dementia incidence, with an adjusted HR of 0.82 (95% CI = 0.78&ndash, 0.87). In a subgroup analysis organized by sex, the differential risk of dementia incidence was assessed in each statin group, implying that sex is an influential factor for the link between statin and dementia. This study suggests that appropriate statin use considering sex differences may have beneficial effects on the development of dementia.

Sixteen of 45 patients with severe fever with thrombocytopenia (36%) were admitted to an intensive care unit; 9 (56%) developed invasive pulmonary aspergillosis (IPA) within a median of 8 days (range, 2–11). Mortality was higher in the IPA vs non-IPA patients and in those without vs with antifungal therapy.