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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]

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]

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: Electromagnetic navigation bronchoscopy (ENB) is an emerging advanced imaging-guided bronchoscopy technique for diagnosing peripheral lung lesions. However, the selection strategy for the optimal biopsy device and whether adopting a multi-tool strategy increases the diagnostic yield remains undetermined. The CONFIDENT-ENB trial (NCT05110131) is a prospective randomized study on ENB, performed in a least-invasive setting. The primary aim is to evaluate whether a combination of needle aspiration and forceps biopsy improves the diagnostic performance, and assess the comparative diagnostic value and discordance of the two devices.Methods: The trial will recruit 142 participants with lung lesions suspected of malignancy who are eligible for an elective ENB procedure under moderate sedation. Participants will undergo ENB-guided needle aspiration and forceps biopsy in a randomized order without the use of any complementary techniques. All participants will be followed up subsequently for up to 12 months to conclude the final diagnosis of the biopsied lesions. Primary outcomes include the diagnostic yield and sensitivity of each biopsy modality and the diagnostic yield of the combined modalities.Discussion: The CONFIDENT-ENB trial will prospectively evaluate the synergistic effectiveness and comparative accuracy of ENB-guided needle aspiration and forceps biopsy in a least-invasive setting. The results are expected to improve our understanding of the optimal tool-selection strategy for ENB.Trial Registration: ClinicalTrials.gov (NCT05110131). Prospectively registered on 5 November 2021. [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]

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]

Traditional beam tracking has severe performance loss under the high mobility and narrow beam scenario. To alleviate the tracking performance degradation, we propose an adaptive beamwidth control for millimeter wave beam tracking. Using the particle filter, we perform the beam tracking, i.e., which is to estimate the channel gain and the angle-of-arrival (AoA). Based on the updated estimate standard deviation of AoA, the adequate beamwidth is set via the partial activation of the antenna array. Simulation results show that the beam tracking with the proposed beamwidth control maintains a higher received signal-to-noise ratio (SNR) than that of the beam tracking without the beamwidth control while the SNR gain leads to a smaller AoA tracking error under high mobility. [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]

In this letter, an electrically small Spidron fractal loop antenna operating in the VHF band is proposed. The ferrite material, which consists of a nickel-zinc combination, is loaded into inside of the loop antenna to increase the gain of the antenna in the low frequency band. To minimize the magnetic loss of the ferrite in the high frequency band, the amount and configuration of the ferrite are optimized using a genetic algorithm. Through this optimization step, the amount of the ferrite is decreased to 37.5% and the gain of the antenna in the high frequency band is improved. The size of the proposed antenna is 0.0242 × 0.0242 × 0.0051 λ L 3 at the lowest operating frequency. The proposed antenna was fabricated to verify the performance, and the simulated and measured results are in good agreement. The measured peak gains varied from −31.6 to −1.9 dBi within the measured frequency band. To examine the performance of the proposed antenna mounted on an unmanned aerial vehicle model (UAV), the antenna on a UAV was also simulated and the results were discussed. The simulated realized peak gains of the antenna on the UAV and on flat ground are similar. [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]

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]

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]

Featured Application: Fuselage mount antenna of an aircraft. A low-profile wideband monocone antenna with bent shorting strips, and parasitic and circular sleeves is proposed. By loading the bent shorting strips, parasitic sleeves, and circular sleeves, miniaturization of the antenna is achieved. Along with bent shorting strips from the monocone hat to the ground plane, parasitic sleeves, and circular sleeves are mounted to enhance the impedance bandwidth. From the experimental results, the –10 dB reflection coefficient bandwidth of the proposed antenna ranges from 810 MHz to 5340 MHz. In addition to the wide bandwidth characteristics, the proposed antenna has highly desirable omnidirectional radiation properties for wireless communication systems. [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]

Purpose: This study was conducted to identify meaning and essential structure of the hospitalization of patients in nursing care integrated service wards of small and medium-size general hospitals. Methods: Experiential data were collected through in-depth interviews with 10 patients who had been hospitalized in nursing care integrated service wards of medium general hospitals. The main question was 'Could you describe your hospitalization experience in nursing care integrated service wards of medium general hospitals?', and collected data were analyzed using Colaizzi's Phenomenological Research Method. Results: Four categories obtained were 'Realize the system that is not established yet', 'Secure care services which are less of a psychological and financial burden', 'Thanks for care providers', and 'Confident of the hopeful system to desire to reuse in the future.' Conclusion: Patients in nursing care integrated service wards of small and medium-size general hospitals were satisfied with the reduction of mental and financial burden caused by nursing and were thankful to nursing staff, who put a lot of efforts into nursing. But, at the same time, they were confused and inconvenienced by the services that were not yet completely established. To improve this situation, it is thought that institutional complements including development of a service standardization manual would be helpful. [ABSTRACT FROM AUTHOR]

Obesity is generally caused by quantitative changes in adipocyte differentiation and fat metabolism. Only a few studies have been determined the effect of red beans extract on obesity and plasma cholesterol concentration. We have been studied the functional activities of red-bean extracts including anti-oxidative effect against DNA and cell damages. Histological study including micro CT analysis showed that the accumulation of fat in hepatocytes and intestines was significantly decreased in red bean extract treated group. In addition, plasma cholesterol and triglyceride levels were decreased in blood samples. In addition, it was confirmed that the red bean extract inhibited the expression of PPARγ, Fabp4 and RETN genes, which regulate total adipocyte differentiation and lipid metabolism. Red bean extract inhibits the expressions of transcription factors associated with adipocyte differentiation in a dose-dependent manner, thereby inhibiting fat accumulation and decreasing blood lipid levels in obese mice induced by high fat diet. [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]

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]

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]

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]

Background: No previous study has employed the frequency and interval of follow-up ultrasonography (US) during the first 10 years after total thyroidectomy in patients with papillary thyroid carcinoma (PTC). The aim of this study was to determine the appropriate frequency and interval of follow-up US during the first 10 years in patients who have undergone total thyroidectomy for PTC. Methods: Two hundred seventy-two patients underwent total thyroidectomy for PTC at our institution from January 2006 to December 2007. Nineteen patients were excluded because of lack of US follow-up data for the neck. Follow-up US was performed by one of two radiologists in all patients. Tumor recurrence/persistence was confirmed by histopathology. Results: The mean interval between surgery and the final follow-up US examination was 79.0 months, and the mean number of follow-up US sessions was 5.9 in the 253 evaluable patients. Eleven patients (4.3%) developed tumor recurrence/persistence, which was detected on follow-up US within 5 years after total thyroidectomy in all cases. T and N stages were independently associated with tumor recurrence/persistence. The interval between surgery and first suspicion of tumor recurrence/persistence on follow-up US was ≤12 months in six patients and 20, 35, 41, 53, and 60 months in the remaining five patients. Conclusion: For detection of tumor recurrence/persistence after total thyroidectomy in patients with PTC, one or two sessions of follow-up US during the first 2 years, depending on T and N stages and one session of follow-up US in every second year during the following 8 years may be appropriate. [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]

Oxidative stress activates macroautophagy/autophagy and contributes to atherogenesis via lipophagic flux, a form of lipid removal by autophagy. However, it is not known exactly how endogenous antioxidant enzymes are involved in lipophagic flux. Here, we demonstrate that the antioxidant PRDX1 (peroxiredoxin 1) has a crucial role in the maintenance of lipophagic flux in macrophages. PRDX1 is more highly expressed than other antioxidant enzymes in monocytes and macrophages. We determined that Prdx1 deficiency induced excessive oxidative stress and impaired maintenance of autophagic flux in macrophages. Prdx1-deficient macrophages had higher intracellular cholesterol mass and lower cholesterol efflux compared with wild type. This perturbation in cholesterol homeostasis was due to impaired lipophagic cholesterol hydrolysis caused by excessive oxidative stress, resulting in the inhibition of free cholesterol formation and the reduction of NR1H3 (nuclear receptor subfamily 1, group H, member 3) activity. Notably, impairment of both lipophagic flux and cholesterol efflux was restored by the 2-Cys PRDX-mimics ebselen and gliotoxin. Consistent with this observation, apoe −/− mice transplanted with bone marrow from prdx1−/−apoe−/− mice had increased plaque formation compared with apoe−/− BM-transplanted recipients. This study reveals that PRDX1 is crucial to regulating lipophagic flux and maintaining macrophage cholesterol homeostasis against oxidative stress. We suggest that PRDX1-dependent control of oxidative stress may provide a strategy for treating atherosclerosis and autophagy-related human diseases. [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]

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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]

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]

Objectives: To evaluate the frequency and clinicopathologic characteristics of RUNX1 mutations, focusing on patients with acute myeloid leukemia not otherwise specified (AML NOS).Methods: Diagnostic samples from 219 patients with AML NOS were analyzed for RUNX1 mutations using standard polymerase chain reaction and direct sequencing.Results: Thirty-one RUNX1 mutations were detected in 33 (15.1%) patients. Mutations clustered in the Runt homology (61.3%) and transactivation domains (25.8%). Frameshift mutations were most common (51.6%), followed by missense (41.9%) and nonsense (6.5%) mutations. Patients with RUNX1 mutations had a lower platelet count (P = .013) and shorter relapse-free survival (P = .045) than those without. The presence of RUNX1 and NPM1 or CEBPA mutations was mutually exclusive. A literature review, including our study, showed that patients with RUNX1 mutations were associated with intermediate risk; coexisting mutations such as FLT3-ITD, ASXL1, TET2, and DNMT3A; and a relatively cytogenetic heterogeneity.Conclusions: Our findings strengthen previous data concerning RUNX1 mutations in AML and support the notion that RUNX1 mutational status should be integrated into a diagnostic workup of AML, particularly for AML NOS or an intermediate-risk group. [ABSTRACT FROM AUTHOR]

Objective. No previous studies regarding the appropriate timing of thyroid hormone discontinuation after hemithyroidectomy have been published. This study aimed to identify the appropriate timing for levothyroxine discontinuation after hemithyroidectomy among patients with papillary thyroid microcarcinoma (PTMC). Methods. This study retrospectively evaluated 304 patients who underwent ≥1 attempt to discontinue levothyroxine after hemithyroidectomy for treating PTMC between January 2008 and December 2013. Fifty-three patients were excluded because of preoperative hypothyroidism or hyperthyroidism, a history of thyroid hormone or antithyroid therapy, no available serological data, or a postoperative follow-up of <24 months. We evaluated the associations of successful levothyroxine discontinuation with patient age, sex, preoperative serological data, underlying thyroid gland histopathology, anteroposterior diameter of the residual thyroid gland, number of discontinuation attempts, and initial discontinuation timing. Results. Among the 251 included patients, 125 patients (49.8%) achieved successful levothyroxine discontinuation during the follow-up period after hemithyroidectomy. There was a significant difference in the outcomes for patients who underwent an initial discontinuation attempt at ≤3 months and ≥4 months after hemithyroidectomy (p < 0.001). There were significant differences in the discontinuation outcomes according to underlying thyroid histopathology (p = 0.001), preoperative thyroid-stimulating hormone levels (p < 0.001), and number of discontinuation attempts (p < 0.001). Conclusions. Among patients with PTMC, the initial levothyroxine discontinuation attempt is recommended at ≥4 months after hemithyroidectomy. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to assess multiple factors influencing the outcomes of ultrasound (US)‐guided fine‐needle aspiration (FNA) of salivary gland lesions. Methods: From 2008 to 2013, a single radiologist performed US‐guided FNA of salivary gland lesions in 243 patients. With the exclusion of pure cysts, poor image quality, and insufficient static image cases, 218 salivary gland lesions in 218 patients were included. The composition, size, location, and vascularity of the lesions were retrospectively investigated on the basis of sonographic findings by the same radiologist. The relationship between sampling adequacy and multiple factors was compared, and the diagnostic accuracy of US‐guided FNA of salivary gland lesions was calculated by using the final diagnosis as a reference standard. Results: The sampling adequacy rate for US‐guided FNA of the 218 salivary gland lesions was 96.8% (211 of 218). A significant difference was observed in the composition and vascularity of the lesions (P <.0001), whereas there was no significant difference in the patient age and sex, lesion size, lesion location, and needle size. The rate of inadequate sampling increased in predominantly cystic lesions compared with solid lesions as well as in low‐vascularity lesions compared with high‐vascularity lesions. Of the 218 lesions, 178 (81.7%) were ultimately diagnosed, and most were benign (162 of 178 [91.0%]). When 3 cases with indeterminate cytologic results were excluded, the sensitivity, specificity, positive and negative predictive values, and accuracy of US‐guided FNA of salivary gland lesions were 64.3%, 98.8%, 81.8%, 97.0%, and 96.0%, respectively. Conclusions: When using US‐guided FNA to diagnose salivary gland lesions, sampling adequacy depends on the composition or vascularity of the lesions. [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]

Purpose: To investigate gray-scale and color Doppler sonographic (US) features of complex fibroadenoma (FA), according to the Breast Imaging-Reporting and Data System (BI-RADS) lexicon.Methods: From 2010 through 2013, 586 women with FAs were seen; 101 (17%) of those lesions were diagnosed as complex FAs on percutaneous needle biopsy or surgery. Among the patients with complex FAs, 67 who had US examination results available were included in this study. In addition, the results from 98 women who had simple FAs were included as controls. US features were retrospectively analyzed by two breast radiologists in consensus for shape, margin, echogenicity, posterior acoustic pattern, boundary, orientation, and associated findings. They also reassessed the BI-RADS category for FAs. Color Doppler US examination results were classified according to the amount of vascularity as absent, moderate, or marked.Results: Complex FA were larger than simple FAs were (14.5 cm versus 12.1 cm, p > 0.05). On univariate analysis, a round to irregular shape, an uncircumscribed margin, the presence of associated findings, and BI-RADS categorization as 4a and 4b were more frequently revealed in complex than in simple FAs (p < 0.05). Multivariate analysis revealed that the tumor margin was a predictive factor for complex FA (odds ratio: 6.08; 95% confidence interval: 1.14-32.49, p < 0.05). On color Doppler US, the complex FAs had higher degrees of vascularity than simple FA (p < 0.05).Conclusions: Complex FAs, in comparison with simple FAs, tend to have more aggressive features and to be in higher BI-RADS categories on US examination. [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]

Fibromatosis refers to an extra-abdominal desmoid tumor or aggressive fibromatosis. Breast fibromatosis can develop in association with the capsule around a breast implant, although reports of cases of fibromatosis associated with breast implants are rare. As the demand for breast augmentation has increased, it is important to understand the diseases associated with breast implants. In the present report, we describe a case of breast fibromatosis that developed adjacent to a breast implant and demonstrated a relatively well-defined border even though it invaded the surrounding structures. We also explore the specific imaging features for diagnosing breast fibromatosis in association with implants by reviewing previous literature. [ABSTRACT FROM AUTHOR]

Spliceosome mutations are associated with myelodysplasia. Here, we aimed to evaluate the frequency and clinical associations of these mutations in 204 patients with acute myeloid leukemia with myelodysplasia-related changes (AML with MRC) and 37 with therapy-related AML (t-AML). The frequency of mutation-positive patients was 17.0%, includingU2AF1(8.3%),SRSF2(5.8%) andSF3B1(2.9%). Mutations were detected almost exclusively in patients with AML with MRC, especially in cases with a preceding myelodysplastic syndrome (MDS) history or myelodysplastic morphology. By contrast, mutations were rare in patients with only MDS-related cytogenetics or t-AML. The presence of a mutation had no impact on survival. In a paired analysis, 16.7% of mutation-negative patients in the MDS phase acquired mutations during leukemogenesis. Our observations highlight the preponderance of spliceosome mutations within a specific AML subgroup with myelodysplasia, and suggest that these mutations might contribute pathologically to leukemogenesis in such patients. [ABSTRACT FROM PUBLISHER]

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]

Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine carcinoma of the skin. MCC is characterized by a high incidence of locoregional recurrence, and distant metastasis, and often requires short-term follow-up after treatment. In this present paper, we describe a rare case of MCC, which presented as a palpable axillary mass and an incidental adrenal mass, and report on the ultrasonography, computed tomography, and 18F-fluorodeoxyglucose-positron emission tomography findings. The patient underwent surgery and adjuvant radiation therapy. Seven months after the initial diagnosis, distant metastasis was detected during a follow-up examination. [ABSTRACT FROM AUTHOR]