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Objectives: To compare the diagnostic performance of gadoxetic acid-enhanced magnetic resonance imaging (MRI), ultrasonography (US)-based elastography, and serologic fibrosis markers in assessing the stage of liver fibrosis., Materials and Methods: This retrospective study included 67 patients (55 male and 12 female; mean age 62.5 years) who underwent gadoxetic acid-enhanced MRI and liver stiffness measurements before liver biopsy or surgery between January 2014 and January 2018. Measurements were performed using transient elastography (TE), ultrasound shear wave elastography point quantification (ElastPQ), and blood tests. The following MRI-based fibrosis markers were assessed: contrast enhancement index (CEI), liver-spleen contrast ratio (LSC), liver-portal vein contrast ratio (LPC), and signal intensity ratio (SIR). The diagnostic performances of fibrosis markers were compared using the area under the receiver operating characteristic curve (AUC), with histopathologic fibrosis stage as the reference standard., Results: The fibrosis stages were F0-F1 (n = 17), F2 (n = 7), F3 (n = 20), and F4 (n = 23). MRI-based fibrosis markers negatively correlated with histologic stage: CEI (r = -0.786); LSC (r = - 0.718); LPC (r = - 0.448); and SIR (r = - 0.617; all P < 0.001). For diagnosis of either significant liver fibrosis (≥ F2) or cirrhosis (F4), the CEI provided better diagnostic accuracy (AUC = 0.898 and 0.881) than the aspartate aminotransferase-to-platelet ratio index (APRI) (AUC = 0.699 and 0.715; all P < 0.05). The CEI displayed similar diagnostic accuracy for ≥ F2 or F4 when using TE (AUC = 0.866 and 0.884, both P > 0.05) or ElastPQ [AUC = 0.751 (P = 0.021) and AUC = 0.786 (P = 0.234)]., Conclusions: The CEI measured by gadoxetic acid-enhanced MRI allows the staging of liver fibrosis, with a diagnostic accuracy comparable to that of TE and superior to that of ElastPQ or APRI.

Thirteen human colorectal cancer (CRC) cell lines were established from 10 primary tumors and 3 metastatic tumors obtained from 13 Korean patients. Characteristics of the cell lines including morphology in vivo and in vitro; mutations of the K-ras, p53, APC and MMR genes and microsatellite instability (MSI) status in vitro were determined. Expression of drug-sensitivity genes including MDR1, MXR, MRP1 and COX2 was also analyzed. The cell lines were unique as judged by DNA fingerprinting using 16 short tandem repeats. Eleven of the cell lines grew as adherent populations and the remaining two as floating aggregates. None of the cell lines were contaminated with Mycoplasma or bacteria. All cell lines showed high viability with relatively long doubling times. Six cell lines contained mutations at K-ras. Seven cell lines displayed p53 gene missense, nonsense and frameshift mutations. MSI was found in three cell lines and two cell lines with an MSI-high phenotype-possessed hMLH1 mutations. Nine cell lines had an APC mutation. MRP1 was highly expressed in all cell lines, and high expression of MDR1, MXR and COX2 evident in eight, six and six cell lines, respectively. Embryonal stem cell markers (MELK, SOX4 and OCT4) were expressed in most of cell lines. The cancer stem cell biomarkers CD133, CD44 and Lgr5 were expressed in 12, 13 and 13 cell lines, respectively. The presently well-characterized CRC cell lines should be useful in investigations of the biological characteristics of CRC, particularly for investigations related to gene alterations associated with CRC and biology of cancer stem cells.

Given the widespread use of whole slide imaging (WSI) for primary pathological diagnosis, we evaluated its utility in assessing histological grade and biomarker expression (ER, PR, HER2, and Ki67) compared to conventional light microscopy (CLM). In addition, we explored the utility of digital image analysis (DIA) for assessing biomarker expression. Three breast pathologists assessed the Nottingham combined histological grade, its components, and biomarker expression through the immunohistochemistry of core needle biopsy samples obtained from 101 patients with breast cancer using CLM, WSI, and DIA. There was no significant difference in variance between the WSI and CLM agreement rates for the Nottingham grade and its components and biomarker expression. Nuclear pleomorphism emerged as the most variable histologic component in intra- and inter-observer agreement (kappa ≤ 0.577 and kappa ≤ 0.394, respectively). The assessment of biomarker expression using DIA achieved an enhanced kappa compared to the inter-observer agreement. Compared to each observer's assessment, DIA exhibited an improved kappa coefficient for the expression of most biomarkers with CLM and WSI. Using WSI to assess prognostic and predictive factors, including histological grade and biomarker expression in breast cancer, is acceptable. Furthermore, incorporating DIA to assess biomarker expression shows promise for substantially enhancing scoring reproducibility. [ABSTRACT FROM AUTHOR]

Aims: We sought to determine which echocardiographic markers of left ventricular (LV) remodeling and diastolic dysfunction can contribute as incremental and independent prognostic information in addition to current clinical risk markers of ischemic LV systolic dysfunction in the Surgical Treatment for Ischemic Heart Failure (STICH) trial.Methods and Results: The cohort consisted of 1511 of 2136 patients in STICH for whom baseline transmitral Doppler (E/A ratio) could be measured by an echocardiographic core laboratory blinded to treatment and outcomes, and prognostic value of echocardiographic variables was determined by a Cox regression model. E/A ratio was the most significant predictor of mortality amongst diastolic variables with lowest mortality for E/A closest 0.8, although mortality was consistently low for E/A 0.6 to 1.0. Mortality increased for E/A < 0.6 and > 1.0 up to approximately 2.3, beyond which there was no further increase in risk. Larger LV end-systolic volume index (LVESVI) and E/A < 0.6 and > 1.0 had incremental negative effects on mortality when added to a clinical multivariable model, where creatinine, LVESVI, age, and E/A ratio accounted for 74% of the prognostic information for predicting risk. LVESVI and E/A ratio were stronger predictors of prognosis than New York Heart Association functional class, anemia, diabetes, history of atrial fibrillation, and stroke.Conclusions: Echocardiographic markers of advanced LV remodeling and diastolic dysfunction added incremental prognostic value to current clinical risk markers. LVESVI and E/A ratio outperformed other markers and should be considered as standard in assessing risks in ischemic heart failure. E/A closest to 0.8 was the most optimal filling pattern. [ABSTRACT FROM AUTHOR]

We report the chloroplast (cp) genome sequence of tartary buckwheat (Fagopyrum tataricum) obtained by next-generation sequencing technology and compared this with the previously reported common buckwheat (F. esculentum ssp. ancestrale) cp genome. The cp genome of F. tataricum has a total sequence length of 159,272 bp, which is 327 bp shorter than the common buckwheat cp genome. The cp gene content, order, and orientation are similar to those of common buckwheat, but with some structural variation at tandem and palindromic repeat frequencies and junction areas. A total of seven InDels (around 100 bp) were found within the intergenic sequences and the ycf1 gene. Copy number variation of the 21-bp tandem repeat varied in F. tataricum (four repeats) and F. esculentum (one repeat), and the InDel of the ycf1 gene was 63 bp long. Nucleotide and amino acid have highly conserved coding sequence with about 98% homology and four genes—rpoC2, ycf3, accD, and clpP—have high synonymous (Ks) value. PCR based InDel markers were applied to diverse genetic resources of F. tataricum and F. esculentum, and the amplicon size was identical to that expected in silico. Therefore, these InDel markers are informative biomarkers to practically distinguish raw or processed buckwheat products derived from F. tataricum and F. esculentum. [ABSTRACT FROM AUTHOR]

Background: The transforming growth factor-β/Smads signaling pathway plays an important role in tumorigenesis and progression in cancer, and may closely be related to the biological behaviors of some malignant tumors, such as gastric carcinoma. In this study, we investigated the roles of Smad3 and Smad3 phosphoisoforms in the prognosis of gastric carcinoma. Methods: We investigated the expressions of Smad3, pSmad3C(S423/425), pSmad3L(T179), pSmad3L(S204), and pSmad3L(S213) in tumor tissue microarrays of 442 gastric carcinoma patients who underwent curative surgery using immunohistochemistry and assessed their correlation with clinical outcome. Results: Positive Smad3 expression was observed in 33.5 % of gastric carcinoma. The rates of positive Smad3 phosphoisoforms expression varied according to the location of phosphorylation within Smad3: pSmad3C(S423/425) 28.5 %, pSmad3L(T179) 5.9 %, pSmad3L(S204) 1.8 %, and pSmad3L(S213) 20.8 %. Positive Smad3 expression was associated with diffuse type ( p = 0.003), poorer histologic differentiation ( p = 0.005), more frequent lymph node metastasis ( p = 0.001), and higher AJCC stage ( p = 0.006). Multivariate analyses revealed that Smad3 expression ( p = 0.041), pSmad3L(T179) expression ( p = 0.011), pSmad3L(S213) expression ( p = 0.003), and American Joint Committee on Cancer (AJCC) stage were independent predictors of shorter disease-free survival. Smad3 expression ( p = 0.033), pSmad3L(T179) expression ( p = 0.012), pSmad3L(S213) expression ( p = 0.005), and AJCC stage were also independent predictors of shorter overall survival. pSmad3C(S423/425) expression tended to show favorable influences on both disease-free survival ( p = 0.134) and overall survival ( p = 0.232). Conclusions: Smad3, pSmad3L(T179), and pSmad3L(S213) expression might be independent predictors of both shorter disease-free survival and shorter overall survival in gastric carcinoma patients after curative surgery, and might help clinicians identify patients at high risk of recurrence. [ABSTRACT FROM AUTHOR]

Summary: Yes-associated protein, a downstream effector of the Hippo signaling pathway, has been linked to progression of non–small-cell lung carcinoma. The aim of this study was to investigate expression of Yes-associated protein in lung adenocarcinoma and squamous cell carcinoma. Associations of Yes-associated protein expression with clinicopathologic parameters, expression of cell cycle–specific markers, and epidermal growth factor receptor gene amplification were also analyzed. In a univariate analysis of the 66 adenocarcinomas, high nuclear expression of Yes-associated protein was significantly correlated with expression of cyclin A and mitogen-activated protein kinase. Multivariate analysis, including age and sex, showed that cyclin A expression was independently correlated with nuclear expression of Yes-associated protein in adenocarcinomas. Furthermore, high nuclear expression of Yes-associated protein was also a significant predictor of epidermal growth factor receptor gene amplification for adenocarcinoma. For the 102 squamous cell carcinomas, univariate analysis revealed that high cytoplasmic expression of Yes-associated protein was correlated with the low pathologic TNM staging (stage I) and histologic grading. Multivariate analysis, including age and sex, showed that cytoplasmic expression of Yes-associated protein was an independent predictor of low pathologic TNM staging. These results indicate that nuclear overexpression of Yes-associated protein contributes to pulmonary adenocarcinoma growth and that high cytoplasmic expression of Yes-associated protein is an independent predictor of low pathologic TNM staging and histologic grading. The differential effects of Yes-associated protein expression patterns in adenocarcinomas and squamous cell carcinomas suggest that Yes-associated protein may play important roles in different pathways in distinct tumor subtypes. These observations may, therefore, lead to new perspectives on therapeutic targeting of these tumor types. [Copyright &y& Elsevier]

Periodontitis is a chronic inflammatory disease caused by the gradual breakdown of tissues surrounding the teeth due to various factors. The disease has been frequently noted in dental outpatients for a number of years. Improvements are required to current diagnostic methods, which have limitations in assessing the condition and progression of periodontitis. The development of diagnostic biomarkers for periodontitis to increase the sensitivity and accuracy of diagnosis is important for the management of periodontitis. In the present study, whole gingival crevicular fluid (GCF) from patients with periodontitis and healthy individuals was characterized via liquid chromatography with tandem mass spectrometry. Label-free quantification was used to identify the differentially abundant protein biomarkers. A total of 1,295 proteins were identified from the whole GCF of patients with periodontitis and healthy individuals via proteomic analysis. When analyzing biological processes, 'metabolic process' and 'cell organization and biogenes' were identified to play important roles in GCF under periodontitis conditions according to Gene Ontology. When analyzing molecular functions, 'catalytic activity' and 'protein binding' were the terms most enriched with differentially abundant proteins under periodontitis conditions. Galectin-10 (Gal-10) was one of the most upregulated proteins in the GCF of patients with periodontitis. The levels of prostaglandin E2 were increased in oral keratinocytes and gingival fibroblasts treated with recombinant (r)Gal-10. The levels of interleukin-8, matrix metalloproteinase 9 and C-reactive protein were increased in the conditioned media (CM) of rGal-10-treated gingival fibroblasts. In addition, the CM of rGal-10-treated gingival fibroblasts induced osteoclast differentiation. These results suggested that Gal-10 expression was increased in the GCF of patients with periodontitis and contributed to the process of osteoclastogenesis. Therefore, Gal-10 may be a candidate biomarker for periodontitis. [ABSTRACT FROM AUTHOR]