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Plant and fruit extracts exhibit fewer side effects than pharmaceuticals and can display therapeutic qualities. Consequently, they have attracted increased attention among health-conscious individuals, and many studies related to their health-promoting effects are being actively conducted. Vitis coignetiae is well-known for its antioxidant, anti-inflammatory, and anticancer properties. However, the immune-enhancing effects of Vitis coignetiae have not yet been studied. In this study, Vitis coignetiae extract (VCE) increased immune-related activity in Wistar rat splenocytes and cyclophosphamide (Cy)-induced immunosuppressed rats. In splenocytes, VCE was nontoxic up to 300 μg/mL and increased cell viability in the presence of Cy. VCE also recovered Cy-induced decreases in cytokine (tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), interleukin-2 (IL-2), and IL-12) levels and natural killer (NK) cell activity in splenocytes. In Cy-induced immunosuppressed rats, VCE protected against Cy-induced spleen tissue damage and decreases in body and spleen weight, cytokine (TNF-α, IFN-γ, IL-2, and IL-12) levels, and NK cell activity. We also observed recovery of immunoglobulin G (IgG) and IgM levels following VCE treatment. In conclusion, the ability of VCE to restore immune activity from an immunosuppressive state to normal levels suggests its immune-enhancing efficacy. Therefore, VCE may have the potential for application in the development of immune-enhancing functional foods and medicines. [ABSTRACT FROM AUTHOR]

Simple Summary: Enzymatic porcine placental hydrolyzing (EPPH) was extracted using enzymatic hydrolysis to extract placental-derived peptides recently reported as excellent bioactive substances, and EPPH was administered to HepG2 cells and alcohol-derived animal models. As a result, it was confirmed that inflammation and antioxidant activity could be regulated through CYP2E1 inhibition. Through these results, we confirmed that the antioxidant and anti-inflammatory effects mediated by CYP2E1 regulation of EPPH have potential for improvement and protection of liver disease in alcoholic liver disease animal models. Alcoholic liver disease is associated with the production of highly reactive free radicals by ethanol and its metabolites. Free radicals not only induce liver oxidation and damage tissues, but also stimulate an inflammatory response in hepatocytes, leading to severe liver disease. In order to improve alcoholic liver disease, enzymatic porcine placenta hydrolysate was studied by exploring various materials. Enzymatic porcine placenta hydrolysate (EPPH) contains various amino acids, peptides, and proteins, and is used as a useful substance in the body. In this study, changes were confirmed in indicators related to the antioxidant efficacy of EPPH in vitro and in vivo. EPPH inhibits an EtOH-induced decrease in superoxide dismutase and catalase activity through inhibition of free radicals without endogenous cytotoxicity. EPPH has been observed to have a partial effect on common liver function factors such as liver weight, ALT, AST, ALP, and GGT. In addition, EPPH affected changes in fat regulators and inflammatory cytokines in blood biochemical assays. It was confirmed that EPPH was involved in fat metabolism in hepatocytes by regulating PPARα in an alcoholic liver disease animal model. Therefore, EPPH strongly modulates Bcl-2 and BAX involved in apoptosis, thereby exhibiting cytochrome P450 (CYP)-inhibitory effects in alcoholic liver disease cells. As a result, this study confirmed that EPPH is a substance that can help liver health by improving liver disease in an alcoholic liver disease animal model. [ABSTRACT FROM AUTHOR]

Curcuma longa and Sargassum coreanum are commonly used in traditional pharmaceutical medicine to improve immune function in chronic diseases. The present study was designed to systematically elucidate the in vitro and in vivo immuno-enhancing effects of a combination of C. longa and S. coreanum extracts (CS) that contain polyphenols and saccharides as functional molecules in a cyclophosphamide (Cy)-induced model of immunosuppression. In primary splenocytes, we observed the ameliorative effects of CS on a Cy-induced immunosuppression model with low cytotoxicity and an optimal mixture procedure. CS treatment enhanced T- and B-cell proliferation, increased splenic natural killer-cell activity, and restored cytokine release. Wistar rats were orally administered low (30 mg/kg), intermediate (100 mg/kg), or high (300 mg/kg) doses of CS for four weeks, followed by oral administration of Cy (5 mg/kg) for four weeks. Compared with the vehicle group, low-, intermediate-, and high-dose CS treatment accelerated dose-dependent recovery of the serum level of tumor necrosis factor-α, interferon-γ, interleukin-2, and interleukin-12. These results suggest that CS treatment accelerates the amelioration of immune deficiency in Cy-treated primary splenocytes and rats, which supports considering it for immunity maintenance. Our findings provide experimental evidence for further research and clinical application in immunosuppressed patients. [ABSTRACT FROM AUTHOR]

BACKGROUND: With an aging society, Korean women ≥70 years of age are increasingly being diagnosed with breast cancer. OBJECTIVE: To investigate the clinicopathological and biological characteristics of breast cancer in elderly Korean women and compare them with breast cancer in elderly (≥70 years) women globally and in Korean women of all ages. METHODS: We retrospectively reviewed the clinicopathological and biological features of breast cancer in elderly Korean women (≥70 years; n = 87) who sought treatment during 2004–2014 from a single institution. These data were indirectly compared with data of Korean women of all ages (nationwide Korean Breast Cancer Registry) or elderly women globally (meta-analysis). RESULTS: Compared to elderly women with breast cancer globally, Korean elderly women had a more symptomatic presentation, lower ER expression, and overexpression or amplification of human epidermal growth factor receptor 2. Compared to Korean women of all ages with breast cancer, elderly Korean women presented with advanced tumor stages, larger tumor size, more lymph node involvement, and more luminal B and basal-like subtypes. CONCLUSIONS: Breast cancer had a more aggressive clinicopathological and biological characteristics in elderly Korean women than in Korean women of all ages or elderly women globally. [ABSTRACT FROM AUTHOR]

Portulaca oleracea L. is a traditional oriental medicine known for its pharmacological effects. The present study aimed to investigate the immunostimulatory effects of PPCE on cyclophosphamide-stimulated rat model and in isolated spleen cells. The result showed that PPCE exerted an immunostimulatory effect in vivo and in vitro. Specifically, PPCE significantly enhanced splenocyte proliferation and upregulated inflammatory cytokines (IL-2, IL-12, TNF-α, and IFN-γ) and NK cell activity in vitro. The immunostimulatory effect was further investigated through various immunological assays. Oral administration of PPCE increased the swimming time and number of immune cells in rats. Histological analysis revealed that PPCE administration exerted splenic recovery. Thus, P. oleracea L. based complex extracts may be used as an immunostimulatory agent in medicine or functional foods. [ABSTRACT FROM AUTHOR]

In this study, we evaluated the immunity-enhancing effects of Orostachys japonicus A. Berger (OJ). To examine the immune protective effect in vitro, primary mouse splenocytes were treated with water or ethanol extracts of OJ in the absence or presence of cyclophosphamide (CY), which is a cytotoxic, immunosuppressive agent. The extracts increased the propagation of splenocytes and inhibited CY-induced cytotoxicity. Further, to examine the immunostimulatory effects in vivo, adult Wistar rats were orally administered OJ extracts with or without CY treatment. With the administration of OJ extracts, CY-treated immunosuppressed rats showed improved physical endurance, as assessed by the forced swim test. In addition, extract administration increased not only the number of immunity-related cells but also the levels of plasma cytokines. OJ extracts also recovered splenic histology in CY-treated rats. These findings suggest that an OJ regimen can enhance immunity by increasing immune cell propagation and specific plasma cytokine levels. [ABSTRACT FROM AUTHOR]

Complex oil of Zanthoxylum schinifolium and Perilla frutescens seed (ZPCO) is used as a traditional medicine due to its pharmacological activities. The aim of this study was to investigate the immunostimulatory effect of ZPCO in isolated splenocytes as well as in an immunosuppressed rat model, which was generated via oral administration of cyclophosphamide. Notably, our results showed that ZPCO exerted an immunity-enhancing effect both in vitro and in vivo. Specifically, ZPCO treatment enhanced the viability and inflammatory cytokine production of splenocytes and NK cell activity in vitro. Moreover, this product improved host defense under immunosuppressive conditions by increasing the number of immune cells and promoting the expression of cytokines involved in immune responses. Our results suggest that complex oil including Z. schinifolium should be explored as a novel immunostimulatory agent that could potentially be used for therapeutic purposes or as an ingredient in functional foods. [ABSTRACT FROM AUTHOR]

Objective: The triple low state [low mean arterial pressure, low bispectral index (BIS) and a low minimum alveolar concentration (MAC)] fraction of anaesthetic during surgery) has been a controversial subject of interest in clinical practise. Previous retrospective studies have produced different conclusions on the association between a triple low state and postoperative 30-day mortality. This study was a systematic review of previous studies on the effects of the triple low state on postoperative 30-day mortality and a meta- analysis with a sample size larger than that of previous studies. Methods: After searching for relevant articles in the PubMed database as on 27 March 2017, we included studies that compared postoperative 30-day mortality between triple low and non-triple low groups. The identified articles were subjected to an initial screening using keywords 'low bispectral index', 'intraoperative hypotension' and 'low minimum alveolar concentration' according to the PRISMA Flow diagram (2009). After a full-text review, appropriate studies were finally included in our meta-analysis. All statistical analyses were performed using the R programme 3.3.2 and meta packages. Results: Three retrospective cohort studies were included in the meta-analysis. The total number of subjects in the triple low and non-triple low groups was 29,402 and 17,428, respectively; the sample size was 46,830. We derived a hazard ratio (HR) of 1.09 [95% confidence interval (CI), 1.07-1.11)] for the fixed effect model and of 1.30 (95% CI, 1.04-1.07) for the random effect model. In the analysis of heterogeneity among the three studies, I2=95% was obtained (P<0.01). Thus, the values obtained from the random effect model were used; HR was 1.30 for the triple low group, indicating a 30% increase in the overall 30-day mortality. Conclusion: The present study demonstrated that patients exposed to the triple low state exhibit higher 30-day mortality rates than those not exposed to the triple low state. [ABSTRACT FROM AUTHOR]

Breast plasmacytoma is an extremely rare tumor. It can occur as a primary isolated tumor or as an extramedullary manifestation in multiple myeloma. This report describes the unusual case of a primary extramedullary plasmacytoma that progressed to multiple myeloma within 15 months in a 35-year-old woman. The patient had been initially diagnosed with a primary extramedullary plasmacytoma of the epidural soft tissue at the cervical 6-thoracic 1 spine level and the stomach. The patient had received chemotherapy and the disease had been in remission. One year later, the disease recurred, affecting both breasts, right clavicle, and orbit. Three months later, the disease had progressed to multiple myeloma. I report this case, focusing on the findings of mammography, ultrasonography, magnetic resonance imaging, and positron emission tomography of bilateral breast plasmacytoma, and provide a review of the literature. [ABSTRACT FROM AUTHOR]

Neurofibromatosis type 1 (NF1) is one of the most common genetic diseases in humans and is associated with various benign and malignant tumors, including breast cancer. However, an increased risk of breast cancer in NF1 patients has not been widely recognized or accepted. Here, we report two cases of breast cancer in NF1 patients and review the literature on the association between NF1 and breast cancer. [ABSTRACT FROM AUTHOR]

Kawasaki disease (KD) is often complicated by coronary artery lesions (CALs), including aneurysms. Because of the complications associated with KD, this disorder is the leading cause of acquired heart disease in children from developed countries. To identify genetic loci that confer a higher risk of developing CALs, we performed a case-control association study using previous genome-wide association study data for samples from KD cases only (n=186) by grouping KD patients without CALs (control: n=123) vs KD patients with extremely large aneurysms (diameter>5 mm) (case: n=17). Twelve loci with one or more sequence variants were found to be significantly associated with CALs (P<1 × 10−5). Of these, an SNP (rs17136627) in the potassium intermediate/small conductance calcium-activated channel, subfamily N, member 2 (KCNN2) at 5q22.3 was validated in 32 KD patients with large aneurysms (diameter>5 mm) and 191 KD patients without CALs (odds ratio (OR)=12.6, Pcombined=1.96 × 10−8). This result indicates that the KCNN2 gene can have an important role in the development of coronary artery aneurysms in KD. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) have been implicated in the pathogenesis and progression of brain tumors. miR-21 is one of the most highly overexpressed miRNAs in glioblastoma multiforme (GBM), and its level of expression correlates with the tumor grade. Programmed cell death 4 (PDCD4) is a well-known miR-21 target and is frequently downregulated in glioblastomas in accordance with increased miR-21 expression. Downregulation of miR-21 or overexpression of PDCD4 can inhibit metastasis. Here, we investigate the role of heterogeneous nuclear ribonucleoprotein C1/C2 (hnRNPC) in the metastatic potential of the glioblastoma cell line T98G. hnRNPC bound directly to primary miR-21 (pri-miR-21) and promoted miR-21 expression in T98G cells. Silencing of hnRNPC lowered miR-21 levels, in turn increasing the expression of PDCD4, suppressing Akt and p70S6K activation, and inhibiting migratory and invasive activities. Silencing of hnRNPC reduced cell proliferation and enhanced etoposide-induced apoptosis. In support of a role for hnRNPC in the invasiveness of GBM, highly aggressive U87MG cells showed higher hnRNPC expression levels and hnRNPC abundance in tissue arrays and also showed elevated levels as a function of brain tumor grade. Taken together, our data indicate that hnRNPC controls the aggressiveness of GBM cells through the regulation of PDCD4, underscoring the potential usefulness of hnRNPC as a prognostic and therapeutic marker of GBM. [ABSTRACT FROM AUTHOR]

Height is a highly heritable trait that involves multiple genetic loci. To identify causal variants that influence stature, we sequenced whole exomes of four children with idiopathic short stature. Ninety-five nonsynonymous single-nucleotide polymorphisms (nsSNPs) were selected as potential candidate variants. We performed association analysis in 740 cohort individuals and identified 11 nsSNPs in 10 loci ( DIS3L2, ZBTB38, FAM154A, PTCH1, TSSC4, KIF18A, GPR133, ACAN, FAM59A, and NINL) associated with adult height ( P < 0.05), including five novel loci. Of these, two nsSNPs ( TSSC4 and KIF18A loci) were significant at P < 0.05 in the replication study ( n = 1,000) and five ( ZBTB38, FAM154A, TSSC4, KIF18A, and FAM59A loci) were significant at P < 0.01 in the combined analysis ( n = 1,740). Together, the five nsSNPs accounted for approximately 2.5% of the height variation. This study demonstrated the utility of next-generation sequencing in identifying genetic variants and loci associated with complex traits. [ABSTRACT FROM AUTHOR]

Abstract: It has been reported that Rhus verniciflua exhibits anti-inflammatory, anti-oxidant and anti-cancer activities. However, little is known about biological activity of sulfuretin, a flavonoid isolated from R. verniciflua. In the present study, we investigated the anti-inflammatory effect and the underlying molecular mechanisms of sulfuretin in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Sulfuretin dose-dependently reduced the productions of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) induced by LPS. Consistent with these findings, sulfuretin significantly suppressed the LPS-induced expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α, and IL-1β. In addition, sulfuretin attenuated LPS-induced DNA binding and the transcriptional activities of nuclear factor-kappa B (NF-κB), which was accompanied by a parallel reduction of degradation and phosphorylation of inhibitory kappa B-α (IκB-α) and consequently by decreased nuclear translocation of p65 subunit of NF-κB. Furthermore, pretreatment with sulfuretin significantly inhibited the LPS-stimulated activation of IκB kinase β (IKKβ). Taken together, these results suggest that the anti-inflammatory effect of sulfuretin in LPS-treated RAW 264.7 macrophages is associated with the suppression of NF-κB transcriptional activity via the inhibitory regulation of IKKβ phosphorylation. [Copyright &y& Elsevier]

Effective beam width model (EBWM) has been widely used for predicting lateral drifts and slab moments in flat slab structures under lateral loads. As the slab moment due to lateral loads increases, slab stiffness decreases due to crack formation. The accuracy of the EBWM strongly depends on how the reduced slab stiffness is estimated. For this purpose, this study developed equations for calculating slab stiffness reduction factor (β) by conducting nonlinear regression analysis using stiffness reduction factors estimated from collected test results. The slab stiffness reduction factor (β) is defined as a ratio of reduced slab stiffness due to crack formation to the stiffness of the uncracked slab section. For verifying the proposed equation, the lateral stiffness of two slab–column connection specimens tested by the writers was compared with the lateral stiffness calculated using the EBWM with the proposed stiffness reduction factor. Further, two flat plate specimens having two continuous spans were also considered for verifying the proposed equations for β. [ABSTRACT FROM AUTHOR]

The trapping of lipid-laden macrophages in the arterial intima is a critical but reversible step in atherogenesis. However, the mechanism by which this occurs is not clearly defined. Here, we tested in mice the hypothesis that CD36, a class B scavenger receptor expressed on macrophages, has a role in this process. Using both in vivo and in vitro migration assays, we found that oxidized LDL (oxLDL), but not native LDL, inhibited migration of WT mouse macrophages but not CD36-deficient cells. We further observed a crucial role for CD36 in modulating the in vitro migratory response of human peripheral blood monocyte-derived macrophages to oxLDL. oxLDL also induced rapid spreading and actin polymerization in CD36-sufficient but not CD36-deficient mouse macrophages in vitro. The underlying mechanism was dependent on oxLDL-mediated CD36 signaling, which resulted in sustained activation of focal adhesion kinase (FAK) and inactivation of Src homology 2-containing phosphotyrosine phosphatase (SHP-2). The latter was due to NADPH oxidase-mediated ROS generation, resulting in oxidative inactivation of critical cysteine residues in the SHP-2-active site. Macrophage migration in the presence of oxLDL was restored by both antioxidants and NADPH oxidase inhibitors, which restored the dynamic activation of FAK. We conclude therefore that CD36 signaling in response to oxLDL alters cytoskeletal dynamics to enhance macrophage spreading, inhibiting migration. This may induce trapping of macrophages in the arterial intima and promote atherosclerosis. [ABSTRACT FROM AUTHOR]

Abstract: The mushroom Inonotus obliquus (Fr.) Pilát (Hymenochaetaceae), has been traditionally used for the treatment of gastrointestinal cancer, cardiovascular disease and diabetes in Russia, Poland and most of Baltic countries. This study was designed to investigate the anti-inflammatory and anti-nociceptive effects of the methanol extract from Inonotus obliquus (MEIO) in vivo and in vitro. MEIO (100 or 200mg/(kgday), p.o.) reduced acute paw edema induced by carrageenin in rats, and showed analgesic activity, as determined by an acetic acid-induced abdominal constriction test and a hot plate test in mice. To reveal the mechanism of the anti-inflammatory effect of MEIO, we examined its effect on lipopolysaccharide (LPS)-induced responses in a murine macrophage cell line RAW 264.7. MEIO was found to significantly inhibit the productions of nitric oxide (NO), prostaglandin E2 (PGE2) and tumor necrosis factor-α (TNF-α) in LPS-stimulated RAW 264.7 macrophages. Consistent with these observations, MEIO potently inhibited the protein and mRNA expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Furthermore, MEIO inhibited the LPS-induced DNA binding activity of nuclear factor-κB (NF-κB), and this was associated with the prevention of inhibitor κB degradation and a reduction in nuclear p65 protein levels. Taken together, our data indicate that the anti-inflammatory and anti-nociceptive properties of MEIO may be due to the inhibition of iNOS and COX-2 expression via the down-regulation of NF-κB binding activity. [Copyright &y& Elsevier]

The combined extracts obtained from three Chinese herb medicine, Kalopanax pictus, Pueraria thunbergiana and Rhus verniciflua, have been used as therapeutics for diabetes mellitus in Korea. In the present study, we have investigated their possible anti-inflammatory effects by comparing the potency of individual extracts with that of the combined extracts. An individual water extract prepared from Kalopanax pictus, Pueraria thunbergiana, and Rhus verniciflua was named K-1, P-1, and R-1, respectively. Simultaneously, we also prepared the combined extracts from above three plant materials by identical methods and named KPR-1. These four extracts were further fractionated into the EtOAc extracts, and these were designated as K-2, P-2, R-2, and KPR-2, respectively. These eight samples were subjected to the nitrite assays in LPS-induced macrophage 264.7 cells. KPR-2 exhibited the most pronounced effect on the inhibition of NO production among all the extracts. KPR-2 also significantly decreased PGE2, and TNF-α release. In addition, KPR-2 showed in vivo anti-inflammatory activity against acute paw edema induced by carrageenan in rats. When analgesic activity was measured by the acetic acid-induced abdominal constriction and hot plate test, KPR-2 showed a dose-dependent inhibition in animal models. These results suggested that the mixture extract and successive fractionation could lead to the better use of anti-inflammatory medicinal crude drugs. [Copyright &y& Elsevier]

To achieve the liver-directed expression in sufficient amounts of therapeutic genes for successful and safe gene therapy, natural liver-specific promoters can be used to direct the expression of therapeutic genes in the liver, whereas strong viral enhancers were used to obtain sufficient amounts of expressed therapeutic gene products. However, very often use of either the former or the latter does not guarantee both potent and liver-specific therapeutic gene expression. Here we conglomerate them and thus create a potent tissue-specific promoter by characterizing and using the liver-type pyruvate kinase proximal promoter (LPKPP) harboring its TATA box and a HNF-1α binding site. Alone it hardly activated its reporter gene expression in non-hepatocytes or hepatocytes. However, in the presence of the SV40 viral enhancer (SV40VE), which is active in multiple cell types, it was able to potently activate its reporter gene expression specifically in hepatocytes. The tissue-specific activation of the LPKPP by the viral enhancer was attributed to HNF-1α binding to the LPKPP. Taken together, these results support the idea that the constitutively active SV40VE could be used to activate the LPKPP in a tissue-specific manner in the presence of HNF-1α. To our knowledge, this is the first study to utilize HNF-1α and its binding site, in the context of the LPKPP, to generate a basal promoter that is transcriptionally activated potently in a tissue-specific manner by a viral enhancer that is active in multiple cell types. [Copyright &y& Elsevier]

In this paper, we report C. agronoma Meyrick for the first time from South Korea. Photographs of adults and genitalia are provided, with brief comments on distribution and biology. [ABSTRACT FROM AUTHOR]

A super-resolution direction-of-arrival (DoA) estimation algorithm that employs a co-prime array and positive atomic norm minimization (ANM) is proposed. To exploit larger array cardinality, the co-prime array vector is constructed by arranging elements of a correlation matrix. The positive ANM is a technique that can enhance resolution when the coefficients of the atoms are the positive real numbers. A novel optimization problem is proposed to ensure the coefficients of the atoms are the positive real numbers, and the positive ANM is employed after solving the optimization problem. The simulation results show that the proposed algorithm achieves high resolution and has lower complexity than the other ANM-based super-resolution DoA estimation algorithm. [ABSTRACT FROM AUTHOR]

This paper introduces a low complexity wideband direction-of-arrival (DOA) estimation algorithm on the co-prime array. To increase the number of the detectable signal sources and to prevent an unnecessary increase in complexity, the low dimensional co-prime array vector is constructed by arranging elements of the correlation matrix at every frequency bin. The atomic norm minimization (ANM)-based approach resolves the grid-mismatch, which causes an inevitable error in the compressive sensing (CS)-based DOA estimation. However, the complexity surges when the ANM is exploited to the wideband DOA estimation on the co-prime array. The surging complexity of the ANM-based wideband DOA estimation on the co-prime array is handled by solving the time-saving semidefinite programming (SDP) motivated by the ANM for multiple measurement vector (MMV) case. Simulation results show that the proposed algorithm has high accuracy and low complexity compared to compressive sensing (CS)-based wideband DOA estimation algorithms that exploit the co-prime array. [ABSTRACT FROM AUTHOR]

Aim: The link between periodontitis and intestinal dysbiosis, two factors that contribute to atherosclerosis, has not been clearly defined. We investigated the integrative effects of oral infection with Porphyromonas gingivalis (PG), the major pathogen for periodontitis, on intestinal microbiota and atherosclerosis. Materials and Methods: ApoE−/− mice were fed a normal chow diet (NC), a Western diet (WD) or a WD with oral PG infection (PG). The PG infection was investigated by placing a total of 109 CFUs of live PG into the oral cavity of each mouse using a feeding needle five times a week for 3 weeks. Atherosclerotic lesions of the aortae were measured, and blood lipoproteins and the expression of molecules related to lipid metabolism in the liver were analysed. We also performed 16S RNA sequencing and a microbiome analysis using faeces. Results: En face bloc preparation of the aortae showed that the PG group had a 1.7‐fold increase in atherosclerotic lesions compared with the WD group (p <.01). Serum analyses showed that oral PG infection induced a significant decrease in high‐density lipoprotein (HDL) and triglyceride. Western blots of hepatic tissue lysates revealed that PG infection reduced the expression of scavenger receptor class B type 1 (SR‐B1) in the liver by 50%. Faecal microbiota analysis revealed that species richness estimates (Chao1, ACE) decreased immediately after PG infection. PG infection also induced a significant decrease in Shannon diversity and an increase in Simpson's indices in the WD‐fed mice. PG infection significantly increased the phyla Actinobacteria and Deferribacteres, along with the species Mucispirillum schaedleri and Lactobacillus gasseri, in the mice. The functional study showed that PG infection increased the expression of proteins that function in carbohydrate and glucose metabolism, including phosphotransferase system (PTS) proteins and the GntR family transcriptional regulator. Conclusions: Oral PG infection promotes atherosclerosis and induces significant metabolic changes, including reduced serum HDL and reduced hepatic SR‐B1 and ABCA1 expression, as well as changes in intestinal microbiota. Our study suggests that intestinal dysbiosis accompanies periodontitis and could play a role in atherosclerosis. [ABSTRACT FROM AUTHOR]

Stress-related cardiomyopathy can develop during the postoperative period due to surgery-related stress factors. However, the prevalence and risk factors for this condition are not yet known. During a retrospective, observational study, patients older than 19 years who underwent procedures from January 2011 to December 2015 at a tertiary hospital were included. The main aim was to identify the prevalence and related risk factors for postoperative stress-related cardiomyopathy. To estimate the incidence per risk factor, univariate and multivariate Poisson regression analyses were performed. During the 5-year period, 95,840 patients older than 19 years underwent 125,314 procedures, and the prevalence of postoperative stress-related cardiomyopathy was 17.74 per 100,000 (95% confidence interval, 9.31–26.17), with an in-hospital mortality of 23.5%. As a result, three risk factors were significantly associated: preoperative American Society of Anesthesiologists classification (incidence rate ratio, 5.901 for American Society of Anesthesiologists class 1–2 [ref] versus 3–6; 95% confidence interval,1.289–27.002; P = 0.022); preoperative body mass index (incidence rate ratio, 1.247 for increases of 18.5 [ref] to 30; 95% confidence interval, 1.067–1.458; P = 0.006); and preoperative serum sodium (incidence rate ratio, 0.830 for each increase of 10 mmol/L from 130; 95% confidence interval, 0.731–0.942; P = 0.004). The incidence rate ratio for age for each increase of 10 years from 50 years was 1.057, but it was not statistically significant (P = 0.064). Our study found that the prevalence of postoperative stress-related cardiomyopathy was 17.74 patients per 100,000 adult patients over the course of 5 years, with four cases of in-hospital mortality. Factors that increased the risk of postoperative stress-related cardiomyopathy included higher American Society of Anesthesiologists class (≥3), preoperative hyponatremia, and higher preoperative body mass index. [ABSTRACT FROM AUTHOR]

Background: Tumor spread through airspaces (STAS) is a recently determined pathologic phenomenon of lung cancer with significant prognostic impact. This study aimed to analyze the unexplored correlation between preoperative biopsy procedure and a higher risk of STAS and its impact on STAS-related outcomes in resected stage I non-small cell lung cancer (NSCLC).Research Question: Does preoperative biopsy procedure affect the risk of STAS and STAS-related outcomes in surgically treated stage I NSCLC?Study Design and Methods: We examined 2,169 patients who underwent surgery for pathologic stage I NSCLC from January 2011 through December 2019 at the Seoul National University Bundang Hospital, a tertiary center in South Korea. Factors including percutaneous needle biopsy (PCNB) and bronchoscopic biopsy were assessed for determining the association between preoperative biopsy procedure and an elevated risk of STAS. In addition, the impact of preoperative biopsy on STAS-related prognosis (recurrence and lung cancer-specific mortality) was evaluated with multivariate Cox regression analyses.Results: STAS findings were positive in 638 of 2,169 patients (29.4%). An insignificant association was found between preoperative biopsy (both PCNB and bronchoscopic biopsy) and STAS. After adjustments for preoperative tumor biopsy, STAS was a significant risk factor for cancer recurrence (hazard ratio [HR], 1.72; 95% CI, 1.20-2.48). Additionally, sublobar resection remained a significant risk factor for recurrence (HR, 3.20; 95% CI, 1.65-6.21) and lung cancer-specific mortality (HR, 12.71; 95% CI, 3.68-43.92) in patients with positive STAS findings. However, this association was insignificant for patients without STAS. Preoperative biopsy was not a significant risk factor for either recurrence and mortality, regardless of STAS positivity.Interpretation: Preoperative biopsy in stage I NSCLC neither was associated with an elevated risk of STAS nor influenced the prognosis related to STAS. Physicians can be less apprehensive about performing preoperative biopsy in relationship to STAS. [ABSTRACT FROM AUTHOR]

Background The distally extended muscle belly of the flexor digitorum (MB-FD) within the carpal tunnel has been suggested as a plausible cause for carpal tunnel syndrome (CTS) based on cadaveric studies. Purpose To evaluate whether MB-FD within the carpal tunnel is a risk factor for CTS by comparing asymptomatic volunteers and patients with CTS. Material and Methods Presence, length, and cross-sectional area of MB-FD within the carpal tunnel were evaluated in 63 wrists of 32 asymptomatic volunteers and 52 wrists of 33 patients with CTS using ultrasonography. Length of MB-FD within the carpal tunnel was measured as the distance between the distal end of MB-FD and the palmar margin of the distal radius longitudinally. On a transverse scan, the cross-sectional area of MB-FD at the proximal limit of the carpal tunnel was measured. Results MB-FD in the carpal tunnel was found in 39 (62%) asymptomatic volunteers and 35 (67%) patients with CTS ( P = 0.549). There was a female preponderancy of MB-FD within the carpal tunnel in asymptomatic volunteers ( P = 0.044), but not in patients. Length and cross-sectional area of MB-FD within the carpal tunnel were significantly greater in male-CTS patients than in male volunteers ( P = 0.022 and 0.012, respectively). These qualities were risk factors for CTS in men, though not in women. Conclusion The presence of distally extended MB-FD within the carpal tunnel was not a risk factor for CTS. In men, a longer and thicker MB-FD within the carpal tunnel increased the risk for CTS. [ABSTRACT FROM AUTHOR]

Atherosclerosis, the major pathology of cardiovascular disease, is caused by multiple factors involving psychological stress. Corticotropin-releasing hormone (CRH), which is released by neurosecretory cells in the hypothalamus, peripheral nerve terminals and epithelial cells, regulates various stress-related responses. Our current study aimed to verify the role of CRH in macrophage foam cell formation, the initial critical stage of atherosclerosis. Our quantitative real-time reverse transcriptase PCR (qRT-PCR), semi-quantitative reverse transcriptase PCR, and Western blot results indicate that CRH down-regulates ATP-binding cassette transporter-1 (ABCA1) and liver X receptor (LXR)-α, a transcription factor for ABCA1, in murine peritoneal macrophages and human monocyte-derived macrophages. Oil-red O (ORO) staining and intracellular cholesterol measurement of macrophages treated with or without oxidized LDL (oxLDL) and with or without CRH (10 nM) in the presence of apolipoprotein A1 (apoA1) revealed that CRH treatment promotes macrophage foam cell formation. The boron-dipyrromethene (BODIPY)-conjugated cholesterol efflux assay showed that CRH treatment reduces macrophage cholesterol efflux. Western blot analysis showed that CRH-induced down-regulation of ABCA1 is dependent on phosphorylation of Akt (Ser473) induced by interaction between CRH and CRH receptor 1(CRHR1). We conclude that activation of this pathway by CRH accelerates macrophage foam cell formation and may promote stress-related atherosclerosis. [ABSTRACT FROM AUTHOR]

Conventional deep learning (DL) algorithm requires full supervision of annotating the region of interest (ROI) that is laborious and often biased. We aimed to develop a weakly-supervised DL algorithm that diagnosis breast cancer at ultrasound without image annotation. Weakly-supervised DL algorithms were implemented with three networks (VGG16, ResNet34, and GoogLeNet) and trained using 1000 unannotated US images (500 benign and 500 malignant masses). Two sets of 200 images (100 benign and 100 malignant masses) were used for internal and external validation sets. For comparison with fully-supervised algorithms, ROI annotation was performed manually and automatically. Diagnostic performances were calculated as the area under the receiver operating characteristic curve (AUC). Using the class activation map, we determined how accurately the weakly-supervised DL algorithms localized the breast masses. For internal validation sets, the weakly-supervised DL algorithms achieved excellent diagnostic performances, with AUC values of 0.92–0.96, which were not statistically different (all Ps > 0.05) from those of fully-supervised DL algorithms with either manual or automated ROI annotation (AUC, 0.92–0.96). For external validation sets, the weakly-supervised DL algorithms achieved AUC values of 0.86–0.90, which were not statistically different (Ps > 0.05) or higher (P = 0.04, VGG16 with automated ROI annotation) from those of fully-supervised DL algorithms (AUC, 0.84–0.92). In internal and external validation sets, weakly-supervised algorithms could localize 100% of malignant masses, except for ResNet34 (98%). The weakly-supervised DL algorithms developed in the present study were feasible for US diagnosis of breast cancer with well-performing localization and differential diagnosis. [ABSTRACT FROM AUTHOR]

Deficiency in DNA damage response (DDR) pathway and accumulation of DNA damage increases mutation rates resulting in genomic instability and eventually increases the risk of cancer. The aim of our study was to investigate expressions of DNA repair genes as new prognostic biomarkers in acute myeloid leukemia (AML). We utilized The Cancer Genome Atlas AML project (TCGA-LAML cohort, 15 acute promyelocytic leukemia (APL) and 155 non-APL AML) for the expression data of DNA repair genes. For validation, clinical samples (Ewha study group, 9 APL and 72 non-APL AML patients) were analyzed for the expression of 22 DNA repair genes using a custom RT2 Profiler PCR Array. APL patients presented significantly lower expression of DNA repair genes than non-APL AML patients in both study groups. Among non-APL AML patients, high expression levels of PARP1, XRCC1, and RAD51 were associated with poor overall survival (OS) probability in both study groups. Furthermore, Cox regression analysis showed that increased expression levels of PARP1, XRCC1, RAD51, BRCA1 and MRE11A could be independent risk factors for OS in the Ewha study group. Among non-APL patients of the Ewha study group, the OS probability of DDR-overexpressed group with at least one gene or more showing Z score greater than 1.5 was poorer than that of DDR non-overexpressed group. In the current study, the DNA repair gene expression profile of APL patients was different from that of non-APL AML patients. Overexpression of DNA repair genes could be a poor prognostic biomarker in non-APL AML. [ABSTRACT FROM AUTHOR]

Abstract: Precise topographic localization, predominance in males mostly of Asian origin, and existence of some familial cases suggest a genetic background for monomelic amyotrophy. To identify susceptibility genes for monomelic amyotrophy, we performed whole-exome sequencing of four unrelated patients with monomelic amyotrophy and detected a total of 45 novel nonsynonymous single-nucleotide polymorphisms as unique variants to monomelic amyotrophy compared to control exomes. Genetic association analysis showed significant association with monomelic amyotrophy in the Gly668Ser variant of the KIAA1377 gene (odds ratio=4.62, P-value=0.0040) and the Pro1794Leu variant of the C5orf42 gene (odds ratio=4.63, P-value=0.0040). Moreover, the combination of two variants increased the risk of monomelic amyotrophy (P =1.4×10−5, OR=61.69, 95% confidence interval=9.62–394.94, in case of combination of two heterozygotes). These data suggest that KIAA1377 and C5orf42 synergistically play a role as susceptibility genes for monomelic amyotrophy. [Copyright &y& Elsevier]

The purpose of this study is to evaluate the seismic performance of gravity-designed post-tensioned flat plate frames with and without slab bottom reinforcement passing through the column. In low and moderate seismic regions, the seismic demands may not control the design, and buildings are often designed considering only gravity loads. This study focuses on the seismic performance of gravity load designed post-tensioned flat plate frames. For this purpose, three-, six- and nine-storey post-tensioned flat plate frames are designed considering only gravity loads. For reinforced concrete flat plate frames, continuous slab bottom reinforcement (integrity reinforcement) passing through the column should be placed to prevent progressive collapse; however, for the post-tensioned flat plate frames, the slab bottom reinforcement is often omitted since the requirement for the slab bottom reinforcement for post-tensioned flat plates is not clearly specified in ACI 318-05. This study evaluates the seismic performance of the model frames by conducting non-linear static pushover analyses and non-linear response history analyses. For conducting non-linear response history analyses, six sets of ground motions are used as input ground motions, which represent two different hazard levels (return periods of 475 and 2475 years) and three different locations (Boston, Seattle and Los Angeles). An analytical model is developed for emulating the non-linear hysteretic behaviour and the failure mechanism of post-tensioned slab-column connections. This study shows that gravity-designed post-tensioned flat plate frames have some seismic resistance. In addition, the seismic performance of post-tensioned flat plate frames is significantly improved by placing slab bottom reinforcement to pass through the column. [ABSTRACT FROM AUTHOR]

Flat plate systems are commonly designed as a gravity-force-resisting system (GFRS) along with stiffer lateral-force-resisting systems (LFRS) such as shear walls, and moment resisting frames; however, deformation compatibility between the GFRS and LFRS results in positive moments (producing tension at the slab bottom) at the slab-column connections in flat plate systems. Continuous slab-bottom reinforcement (integrity reinforcement) passing through the column is required to prevent progressive collapse; however, for posttensioned flat plate (PT-flat plate) systems, there have been arguments among engineers on applying continuous slab-bottom reinforcement since ACI 318 and 352 provisions do not clearly specify the requirement on the slab-bottom reinforcement for PT flat plates. The purpose of this study is to investigate the effects of continuous slab-bottom reinforcement passing through the column core on the hysteretic behavior of the PT slab-column connections. Test results for six, 3/5 scaled specimens for interior PT flat plate connections subjected to constant gravity loads and quasistatic reversed cyclic lateral loads are presented and indicate that the slab-bottom reinforcement conforming to ACI-ASCE 352R.1 is not required to prevent collapse, but does significantly improves the hysteretic energy absorption capacity. [ABSTRACT FROM AUTHOR]

Abstract: The purpose of this study is to evaluate hysteretic behavior of exterior post-tensioned flat plate slab–column connections (PT connections) designed to resist only gravity loads. For this purpose, experimental studies were conducted using three approximately two-thirds-scale test specimens; two exterior PT connection specimens having different tendon layouts and one exterior reinforced concrete flat plate slab–column connection (RC connection) specimen. Quasi-static cyclic loading was applied to the specimen with a constant gravity load. All specimens had bottom bonded reinforcement around the column as required by ACI 352.1R-89. This study collects previous test results to draw a general conclusion for the hysteretic behavior of the PT exterior connections. This study observed that the tendon layout influenced the hysteretic behavior of PT exterior connections, which means that lateral drift capacity, dissipated energy, failure mechanism, and ductility vary with respect to tendon layouts. Moreover, this study shows that the amount of bottom reinforcement specified by the ACI 352.1R-89 is sufficient for resisting positive moments resulting from moment reversal under the cyclic loading. Shear strength of the test specimens is more accurately predicted by the shear strength equation considering average compressive strength due to post-tensioning tendons than that without considering . [Copyright &y& Elsevier]

Abstract: The anti-inflammatory effects of caffeic acid (CA), caffeic acid methyl ester (CM) and di-O-acetylcaffeic acid (DAC) were investigated in rats using the carrageenin-induced edema model and the antinociceptive effects of these compounds were also assessed in mice by means of the acetic acid-induced abdominal constriction test and hot plate test. CM (10mg/kg, p.o.) showed the most potent anti-inflammatory and antinociceptive effects in these animal models. To investigate the mechanism of the anti-inflammatory action, we examined the effects of these compounds on the lipopolysaccaride (LPS)-induced NO and PGE2 responses in the murine macrophage cell line, RAW 264.7. Our data indicate that CM is the most potent inhibitor of NO and PGE2 production and it also significantly decreased tumor necrosis factor-alpha (TNF-α) release. Consistent with these observations, the protein and mRNA expression levels of iNOS and COX-2 were found to be inhibited by CM in a dose-dependent manner. Furthermore, CM inhibited the nuclear factor-κB (NF-κB) activation induced by LPS, which was associated with the prevention of the degradation of the inhibitor κB, and subsequently with decreased p65 protein levels in the nucleus. Taken together, our data indicate that the anti-inflammatory properties of CM might result from the inhibition of iNOS, COX-2 and TNF-α expression through the down-regulation of NF-κB binding activity. [Copyright &y& Elsevier]

Background: Macrophages produce many inflammation-associated molecules, released by matrix metalloproteinases, such as adhesion molecules, and cytokines, as well, which play a crucial role in atherosclerosis. In this context, we investigated the relationship between Ninjurin-1 (Ninj1 [nerve injury-induced protein]), a novel matrix metalloproteinase 9 substrate, expression, and atherosclerosis progression.Methods: Ninj1 expression and atherosclerosis progression were assessed in atherosclerotic aortic tissue and serum samples from patients with coronary artery disease and healthy controls, and atheroprone apolipoprotein e-deficient (Apoe-/-) and wild-type mice, as well. Apoe-/- mice lacking systemic Ninj1 expression (Ninj1-/-Apoe-/-) were generated to assess the functional effects of Ninj1. Bone marrow transplantation was also used to generate low-density lipoprotein receptor-deficient (Ldlr-/-) mice that lack Ninj1 specifically in bone marrow-derived cells. Mice were fed a Western diet for 5 to 23 weeks, and atherosclerotic lesions were investigated. The anti-inflammatory role of Ninj1 was verified by treating macrophages and mice with the peptides Ninj11-56 (ML56) and Ninj126-37 (PN12), which mimic the soluble form of Ninj1 (sNinj1).Results: Our in vivo results conclusively showed a correlation between Ninj1 expression in aortic macrophages and the extent of human and mouse atherosclerotic lesions. Ninj1-deficient macrophages promoted proinflammatory gene expression by activating mitogen-activated protein kinase and inhibiting the phosphoinositide 3-kinase/Akt signaling pathway. Whole-body and bone marrow-specific Ninj1 deficiencies significantly increased monocyte recruitment and macrophage accumulation in atherosclerotic lesions through elevated macrophage-mediated inflammation. Macrophage Ninj1 was directly cleaved by matrix metalloproteinase 9 to generate a soluble form that exhibited antiatherosclerotic effects, as assessed in vitro and in vivo. Treatment with the sNinj1-mimetic peptides, ML56 and PN12, reduced proinflammatory gene expression in human and mouse classically activated macrophages, thereby attenuating monocyte transendothelial migration. Moreover, continuous administration of mPN12 alleviated atherosclerosis by inhibiting the enhanced monocyte recruitment and inflammation characteristics of this disorder in mice, regardless of the presence of Ninj1.Conclusions: Ninj1 is a novel matrix metalloproteinase 9 substrate in macrophages, and sNinj1 is a secreted atheroprotective protein that regulates macrophage inflammation and monocyte recruitment in atherosclerosis. Moreover, sNinj1-mediated anti-inflammatory effects are conserved in human macrophages and likely contribute to human atherosclerosis. [ABSTRACT FROM AUTHOR]

Conventionally, apnea–hypopnea index (AHI) is used to define and categorize the severity of obstructive sleep apnea. However, routine polysomnography (PSG) includes multiple parameters for assessing the severity of obstructive sleep apnea. The goal of this study is to identify and categorize obstructive sleep apnea phenotypes using unsupervised learning methods from routine PSG data. We identified four clusters from 4,603 patients by using 29 PSG variable and arranged according to their mean AHI. Cluster 1, spontaneous arousal (mean AHI = 8.52/h); cluster 2, poor sleep and periodic limb movements (mean AHI = 12.16/h); cluster 3, hypopnea (mean AHI = 38.60/h); and cluster 4, hypoxia (mean AHI = 69.66/h). Conventional obstructive sleep apnea classification based on apnea–hypopnea index severity showed no significant difference in cardiovascular or cerebrovascular mortality (Log rank P = 0.331), while 4 clusters showed an overall significant difference (Log rank P = 0.009). The risk of cardiovascular or cerebrovascular mortality was significantly increased in cluster 2 (hazard ratio = 6.460, 95% confidence interval 1.734–24.073) and cluster 4 (hazard ratio = 4.844, 95% confidence interval 1.300–18.047) compared to cluster 1, which demonstrated the lowest mortality. After adjustment for age, sex, body mass index, and underlying medical condition, only cluster 4 showed significantly increased risk of mortality compared to cluster 1 (hazard ratio = 7.580, 95% confidence interval 2.104–34.620). Phenotyping based on numerous PSG parameters gives additional information on patients' risk evaluation. Physicians should be aware of PSG features for further understanding the pathophysiology and personalized treatment. [ABSTRACT FROM AUTHOR]

Activated macrophages show increased expression of vimentin, an intermediate filament protein. Macrophages secrete vimentin into extracellular space; however, the functions of extracellular vimentin and the process of vimentin secretion are not clearly defined. We found that oxidized low-density lipoproteins (oxLDL) via CD36 induced vimentin secretion in macrophages. We also revealed that extracellular vimentin induced macrophages to release inflammatory cytokines and augmented oxLDL-induced release of TNF-α and IL-6. Extracellular vimentin activated NF-κB signaling via phosphorylation of focal adhesion kinase (p-FAK) and IκB kinase (p-IκK). Extracellular vimentin also amplified the oxLDL-induced p-IκK increase and IκB decrease. Vimentin-induced TNF-α release was not dependent on Dectin-1, which is known to bind vimentin. We measured serum vimentin concentrations and found that patients with atherosclerotic coronary artery disease had higher levels of serum vimentin than normal subjects. Circulating oxLDL and vimentin concentrations showed a high degree of correlation. In mouse experiments, vimentin concentration was higher in the sera of apoE null mice with western diet–induced atherosclerosis than in the sera of chow diet–fed apoE null mice without atherosclerosis. We concluded that vimentin is secreted by oxLDL/CD36 interaction in macrophages and extracellular vimentin promotes macrophage release of pro-inflammatory cytokines. This may contribute to atherosclerotic inflammation and based on our analysis of serum vimentin, we suggest serum vimentin as a predictive marker for atherosclerosis. Key messages: OxLDL via CD36 induces secretion of vimentin, a cytoskeletal protein in macrophages. Extracellular vimentin induces macrophages to release proinflammatory cytokines such as tumor necrotizing factor-alpha (TNF-α) and this process is mediated by activation of focal adhesion kinase (FAK) and NF-ƙB signaling. Serum concentrations of vimentin in coronary artery disease patients are higher than that in control group. Vimentin concentration is strongly correlated with oxLDL concentration in serum. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine whether disease recurrence and intrinsic characteristics of ductal carcinoma in situ (DCIS) are associated with the imaging method of detection in asymptomatic women. This multicenter, retrospective study included 844 women treated for asymptomatic DCIS who had pre-operative mammography and breast ultrasonography (US) studies available. Of the 844 women, 25 (3.0%) developed recurrences. Patients in the US group had significantly lower 5- and 10-y recurrence-free survival (RFS) rates compared with patients in the mammography group (p = 0.011). US-detected DCIS showed significantly lower 5-and 10-y RFS rates compared with mammography-detected DCIS in patients <50 y or with mammographically dense breasts (p = 0.002 and 0.002, respectively). US as the detection modality (hazard ratio [HR]: 4.451; 95% confidence interval [CI]: 1.530, 12.950; p = 0.006) and HER2 positivity (HR: 4.036; 95% CI: 1.438; 11.330; p = 0.008) were significantly associated with recurrence. We concluded that US as the detection modality and HER2 positivity were significantly associated with recurrence in patients treated for asymptomatic DCIS. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the effect of training radiology residents on breast ultrasonography (US) according to the Breast Imaging Reporting And Data System (BI-RADS) and the factors that influence the training effect.Methods: This multicenter, prospective study was approved by eight institutional review boards. From September 2013 to July 2014, 248 breast masses in 227 women were included for US image acquisition. Representative B-mode and video images of the breast masses were recorded, among which 54 cases were included in the education set and 66 in the test set. Sixty-one radiology residents scheduled for breast imaging training individually reviewed the test set, immediately before, 1 month after, and 6 months after training. Diagnostic performances and US descriptors of the residents were evaluated and compared against those of expert radiologists.Results: Agreements between residents and experienced radiologists showed improvement after training, while agreements between post-training and post-6-month training descriptors did not show significant differences (all p > 0.05, respectively). Sensitivity, negative predictive value (NPV), and AUC were significantly improved for residents post-training and post-6-month training (all p < 0.05), while approximating the performances of expert radiologists except for AUC (0.836, 0.840, and 0.908, respectively, p < 0.05). Low levels of pre-training AUC, total number of breast US examinations, and the number of sessions per week that residents were involved in were factors influencing the improvement of AUC.Conclusion: Training using education material dedicated for breast US imaging effectively improved the diagnostic performances of radiology residents and agreements with experienced radiologists on US BI-RADS features.Key Points: • Agreements on lesion descriptors between residents and experienced radiologists showed improvement after training, regardless of test point. • Sensitivity, NPV, and AUC were significantly improved for residents in post-training and post-6-month training (all p < 0.05). • Low levels of pre-training AUC, total number of breast US examinations, and the number of sessions per week that residents were involved in were factors influencing the improvement of AUC. [ABSTRACT FROM AUTHOR]

The incidence rate of breast fibroadenomas is higher among female kidney transplant (KT) patients treated using cyclosporine (CsA) for immunosuppression than in the general population. As such, there is an effort to convert immunosuppression from CsA or tacrolimus to sirolimus. Our aim was to assess the reversibility of a breast fibroadenoma after conversion in a small cohort of female KT recipients. This was an open-label, single-arm study including 128 female KT recipients, with a positive finding of a breast fibroadenoma in 15. Lesions were classified according to the Breast Imaging Reporting and Data System (BIRADS). Among these 15, a total of 7 converted from tacrolimus to sirolimus and 8 converted from CsA. We measured the change in BIRADS category and hormone and cytokine levels from baseline to 12 months after conversion. The primary outcome was progression or reversal of existing fibroadenomas at 12 months after conversion. Secondary outcomes were differences in hormone and cytokine levels. Conversion from CsA or tacrolimus to sirolimus had no significant effect on the BIRADS classification. However, conversion to sirolimus did produce a significant decrease in the level of transforming growth factor β cytokine, this level being closely associated with fibroadenomas. Conversion from a calcineurin inhibitor to sirolimus can block the progression of fibroadenomas. Further research is needed to confirm our results. • Cyclosporine after kidney transplant increases the risk of breast fibroadenoma. • Conversion from cyclosporine or tacrolimus to sirolimus can lower this risk. • Among 15 women with breast fibroadenoma, conversion did not change the Breast Imaging Reporting and Data System class. • Conversion did lower transforming growth factor βl level, which is associated with breast fibroadenoma. [ABSTRACT FROM AUTHOR]

A 18–40 GHz wideband substrate integrated waveguide (SIW) H-plane horn antenna is proposed for applications on both the K- and Ka-bands. By employing a grating transition in front of the horn aperture, the impedance bandwidth (IBW) of the proposed antenna is broadened considerably. A broadband double-ridge waveguide (DRW)-to-SIW transition is also developed as the feeding structure for the proposed SIW H-plane horn antenna. The DRW is adopted to support a wider IBW as compared to that of a rectangular waveguide. A prototype of the proposed antenna is experimentally verified. The measured results show that the IBW for $|S_{11}| \leq -10$ dB ranges from 18 GHz to more than 40 GHz, covering the entire K- and Ka-bands. The measured gain varies from 7.52 to 15.37 dBi with an average gain of 11.58 dBi. In addition, the endfire radiation patterns are observed and maintained within the IBW. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer with lymphoid stroma (GCLS) is pathologically characterized by poorly developed tubular structures with a prominent lymphocytic infiltration. Its clinical and prognostic features differ in patients positive and negative for Epstein-Barr virus (EBV) infection. This study analyzed the expression of programmed cell death-1 (PD-1), programmed cell death ligand-1 (PD-L1), and the density of tumor-infiltrating lymphocytes (TILs) including CD3+ and CD8+ T cells, as well as their prognostic significance in patients with GCLS.Methods: The study included 58 patients with GCLS (29 EBV+ and 29 EBV−) who underwent curative resection. Expression of CD3, CD8, PD-1, and PD-L1 in tumor cells and TILs was analyzed using a quantitative multispectral imaging system (Opal™), with these results validated by immuno-histochemical assays for PD-L1 on whole slide sections.Results: The proportion of tumors overexpressing PD-L1 (31.0 vs. 0%, P = 0.002), TIL density (4548 vs. 2631/mm2, P < 0.001), and intra-tumoral CD8+ T-cell density (2650 vs. 1060/mm2, P < 0.001) were significantly higher in EBV+ than in EBV− GCLS. In addition, CD8+/CD3+ T-cell ratio was higher in EBV+ than in EBV− GCLS (55.3 vs. 35.8%, P < 0.001). Lower TIL density, defined as < 1350/mm2, was a significant negative factor of survival.Conclusions: Despite histopathological similarity, quantitative multispectral imaging revealed differences in the tumor immune micro-environment between EBV+ and EBV− GCLS, indicating that the underlying pathogenesis differs in these two disease entities. TIL density may be a prognostic marker in patients with GCLS. [ABSTRACT FROM AUTHOR]

This study investigated the role of BRAF mutation analysis in thyroid fine-needle aspiration (FNA) samples compared to ultrasonographic and cytological diagnoses. A total 316 patients underwent ultrasonography (US)-guided FNA with BRAFV600E mutation analysis to diagnose thyroid nodules. One hundred sixteen patients with insufficient US images (n = 6), follow-up loss (n = 43), or unknown final diagnosis (n = 67) were excluded from the study. Comparisons between US diagnoses, cytological diagnoses, and BRAF mutation analysis were performed. Of 200 thyroid nodules, there was US diagnosis with 1 false negative and 11 false positive cases, cytological diagnosis with 10 false negative and 2 false positive cases, and BRAFV600E mutation analysis with 19 false negative and 2 false positive cases. The sensitivity, specificity, positive and negative predictive values, and accuracy of BRAFV600E mutation analysis were 83.2%, 98.1%, 97.5%, 86.6%, and 91%, respectively. Of the 18 nodules with Bethesda category III, 9 were true positive, 6 were true negative, 3 was a false negative, and none were false positive on BRAF mutation analysis. In conclusion, we recommend that BRAFV600E mutation analysis only be performed for evaluating thyroid nodules with Bethesda category III, regardless of US diagnosis. [ABSTRACT FROM AUTHOR]

The cross ambiguity function (CAF) has been commonly used to find time difference of arrival (TDOA) and frequency difference of arrival (FDOA). In most cases, direct computation of the CAF by using a conventional method such as fast Fourier transform is too computationally intensive. Thus, a two-stage approach consisting of a coarse mode to find rough TDOA/FDOA estimates and a fine mode for precise estimation was introduced. However, there has been no methodology for selecting an interpolation factor determined by the sampling frequency and target precision which significantly affects the computational complexity. In addition, even if the computational complexity can be reduced by using the optimal interpolation factor, the huge transmission data through the datalink between sensors and the central station still remains to be an obstacle for an electronic warfare (EW) system. In this respect, we derive an optimal interpolation factor and then propose a new two-stage TDOA/FDOA estimation algorithm using a resampling block to reduce the computational complexity and the data size simultaneously in EW systems. In the proposed method, the optimal interpolation factor can be used irrespective of the sampling frequency and the target precision. Simulation results show that the optimal interpolation factor efficiently reduces the computational burden without the loss of estimation performance. [ABSTRACT FROM AUTHOR]

Consumption of a typical Western diet is a risk factor for several disorders. Metabolic syndrome is the most common disease associated with intake of excess fat. However, the incidence of inflammatory bowel disease is also greater in subjects consuming a Western diet, although the mechanism of this phenomenon is not clearly understood. We examined the morphological and functional changes of the intestine, the first site contacting dietary fat, in mice fed a high-fat diet (HFD) inducing obesity. Paneth cell area and production of antimicrobial peptides by Paneth cells were decreased in HFD-fed mice. Goblet cell number and secretion of mucin by goblet cells were also decreased, while intestinal permeability was increased in HFD-fed mice. HFD-fed mice were more susceptible to experimental colitis, and exhibited severe colonic inflammation, accompanied by the expansion of selected pathobionts such as Atopobium sp. and Proteobacteria. Fecal microbiota transplantation transferred the susceptibility to DSS-colitis, and antibiotic treatment abrogated colitis progression. These data suggest that an experimental HFD-induced Paneth cell dysfunction and subsequent intestinal dysbiosis characterized by pathobiont expansion can be predisposing factors to the development of inflammatory bowel disease. [ABSTRACT FROM AUTHOR]