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Iczkowski K.A.,Medical College of Wisconsin | Egevad L.,Karolinska Institutet | Ma J.,Bostwick Laboratories Inc. | Harding-Jackson N.,Medical College of Wisconsin | And 36 more authors.
Annals of Diagnostic Pathology | Year: 2014

The diagnosis of intraductal carcinoma (IDC) of the prostate remains subjective because 3 sets of diagnostic criteria are in use. An internet survey was compiled from 38 photomicrographs showing duct proliferations: 14 signed out as high-grade prostatic intraepithelial neoplasia (HGPIN), 17 IDC, and 7 invasive cribriform/ductal carcinoma. Each image was assessed for the presence of 9 histologic criteria ascribed to IDC. Thirty-nine respondents were asked to rate images as (1) benign/reactive, (2) HGPIN, (3) borderline between HGPIN and IDC, (4) IDC, or (5) invasive cribriform/ductal carcinoma. Intraclass correlation coefficient was 0.68. There was 70% overall agreement with HGPIN, 43% with IDC, and 73% with invasive carcinoma (P < .001, X2). Respondents considered 19 (50%) of 38 cases as IDC candidates, of which 5 (26%) had a two-thirds consensus for IDC; two-thirds consensus for either borderline or IDCwas reached in 9 (47%). Two-thirds consensus other than IDCwas reached in the remaining 19 of 38 cases, with 15 supporting HGPIN and 4 supporting invasive carcinoma. Findings that differed across diagnostic categories were lumen-spanning neoplastic cells (P < .001), 2× benign duct diameters (P < .001), duct space contours (round, irregular, and branched) (P < .001), papillary growth (P = .048), dense cribriform or solid growth (both P = .023), and comedonecrosis (P = .015). When the 19 of 38 images that attained consensus for HGPIN or invasive carcinoma were removed from consideration, lack of IDC consensus was most often attributable to only loose cribriform growth (5/19), central nuclear maturation (5/19), or comedonecrosis (3/19). Of the 9 histologic criteria, only 1 retained significant correlation with a consensus diagnosis of IDC: the presence of solid areas (P =.038). One case that attained IDC consensus had less than 2× duct enlargement yet still had severe nuclear atypia and nucleomegaly. Six fold nuclear enlargement was not significant (P=.083), although no image had both 6× nuclei and papillary or loose cribriform growth: a combination postulated as sufficient criteria for IDC. Finally, 20.5% of respondents agreed that an isolated diagnosis of IDC on needle biopsy warrants definitive therapy, 20.5% disagreed, and 59.0% considered the decision to depend upon clinicopathologic variables. Although IDC diagnosis remains challenging, we propose these criteria: a lumen-spanning proliferation of neoplastic cells in preexisting ducts with a dense cribriform or partial solid growth pattern. Solid growth, in any part of the duct space, emerges as the most reproducible finding to rule in a diagnosis of IDC. Comedonecrosis is a rarer finding, but in most cases, it should rule in IDC. Duct space enlargement to greater than 2× the diameter of the largest, adjacent benign spaces is usually present in IDC, although there may be rare exceptions. © 2014 Elsevier Inc. All rights reserved. Source

Wu W.,U.S. National Center for Atmospheric Research | Liu Y.,U.S. National Center for Atmospheric Research | Ge M.,U.S. National Center for Atmospheric Research | Rostkier-Edelstein D.,Israel Institute of Biology Research | And 6 more authors.
Atmospheric Research | Year: 2012

Most of the annual rainfall in the Southeastern Mediterranean falls in the wet season from November to March. It is associated with Mediterranean cyclones, and is sensitive to climate variability. Predicting the wet season precipitation with a few months advance is highly valuable for water resource planning and climate-associated risk management in this semi-arid region. The regional water resource managements and climate-sensitive economic activities have relied on seasonal forecasts from global climate prediction centers. However due to their coarse resolutions, global seasonal forecasts lack regional and local scale information required by regional and local water resource managements. In this study, an analog statistical-downscaling algorithm, k-nearest neighbors (KNN), was introduced to bridge the gap between the coarse forecasts from global models and the needed fine-scale information for the Southeastern Mediterranean. The algorithm, driven by the NCEP Climate Forecast System (CFS) operational forecast and the NCEP/DOE reanalysis, provides monthly precipitations at 2-4. months of lead-time at 18 stations within the major regional hydrological basins. Large-scale predictors for KNN were objectively determined by the correlations between the station historic daily precipitation and variables in reanalysis and CFS reforecast. Besides a single deterministic forecast, this study constructed sixty ensemble members for probabilistic estimates. The KNN algorithm demonstrated its robustness when validated with NCEP/DOE reanalysis from 1981 to 2009 as hindcasts before applied to downscale CFS forecasts. The downscaled predictions show fine-scale information, such as station-to-station variability. The verification against observations shows improved skills of this downscaling utility relative to the CFS model. The KNN-based downscaling system has been in operation for the Israel Water Authority predicting precipitation and driving hydrologic models estimating river flow and aquifer charge for water supply. © 2012. Source

Song J.Y.,Korea University | Song J.Y.,Transgovernmental Enterprise for Pandemic Influenza in Korea | Cheong H.J.,Korea University | Lee J.,Hallym University | And 11 more authors.
Vaccine | Year: 2015

Background: Cell culture-derived influenza vaccines (CCIVs) have several important advantages over egg-based influenza vaccines, including shorter production time, better preservation of wild-type virus antigenicity and large-scale production capacity. Methods: A randomized, double-blind, phase 3 trial was undertaken to evaluate the immunogenicity and safety of a novel cell culture-derived inactivated, subunit, trivalent influenza vaccine (NBP607, SK Chemicals, Seongnam, Korea) compared to the control vaccine (Agrippal®S1, Novartis Vaccines and Diagnostics Srl, Siena, Italy) among healthy adults aged 19 years or older (Clinical trial Number-NCT02344134). Immunogenicity was determined at pre-vaccination, 1 month and 6 month post-vaccination by the hemagglutination inhibition assay. Solicited and unsolicited adverse events were assessed after vaccination. Results: A total of 1156 healthy subjects were recruited. NBP607 met all of the criteria of Committee for Medicinal Products for Human Use (CHMP) at 21 days post-vaccination. Contrary to NBP607, the control vaccine did not satisfy the seroconversion criteria for influenza B irrespective of age. Although the geometric mean titer for each influenza subtype declined gradually, seroprotection rate still remained ≥80% for all subtypes up to six month after NBP607 administration. NBP607 recipients met the seroprotection criteria for all three influenza subtypes up to 6 month post-vaccination. There was no significant difference in the occurrence of adverse events between the NBP607 and control groups. Conclusion: NBP607, a novel CCIV, showed excellent immunogenicity that lasted ≥6 months after vaccination and had tolerable safety profiles. In particular, NBP607 was more immunogenic against influenza B compared to the control, an egg-based subunit vaccine. © 2015 Elsevier Ltd. Source

Saika H.,Japan National Institute of Agrobiological Science | Horita J.,Life Science Research Institute | Taguchi-Shiobara F.,Japan National Institute of Agrobiological Science | Nonaka S.,University of Tsukuba | And 11 more authors.
Plant Physiology | Year: 2014

Target-site and non-target-site herbicide tolerance are caused by the prevention of herbicide binding to the target enzyme and the reduction to a nonlethal dose of herbicide reaching the target enzyme, respectively. There is little information on the molecular mechanisms involved in non-target-site herbicide tolerance, although it poses the greater threat in the evolution of herbicide-resistant weeds and could potentially be useful for the production of herbicide-tolerant crops because it is often involved in tolerance to multiherbicides. Bispyribac sodium (BS) is an herbicide that inhibits the activity of acetolactate synthase. Rice (Oryza sativa) of the indica variety show BS tolerance, while japonica rice varieties are BS sensitive. Map-based cloning and complementation tests revealed that a novel cytochrome P450 monooxygenase, CYP72A31, is involved in BS tolerance. Interestingly, BS tolerance was correlated with CYP72A31 messenger RNA levels in transgenic plants of rice and Arabidopsis (Arabidopsis thaliana). Moreover, Arabidopsis overexpressing CYP72A31 showed tolerance to bensulfuron-methyl (BSM), which belongs to a different class of acetolactate synthase-inhibiting herbicides, suggesting that CYP72A31 can metabolize BS and BSM to a compound with reduced phytotoxicity. On the other hand, we showed that the cytochrome P450 monooxygenase CYP81A6, which has been reported to confer BSM tolerance, is barely involved, if at all, in BS tolerance, suggesting that the CYP72A31 enzyme has different herbicide specificities compared with CYP81A6. Thus, the CYP72A31 gene is a potentially useful genetic resource in the fields of weed control, herbicide development, and molecular breeding in a broad range of crop species. © 2014, American Society of Plant Biologists. All Rights Reserved. Source

Yang H.,Guangxi Medical University | Yang H.,Guangxi University | Qiu Y.,Guangxi Medical University | Zeng X.,Guangxi Medical University | And 4 more authors.
Experimental and Therapeutic Medicine | Year: 2016

The aim of the present study was to investigate the effects of feeder layers composed of various ratios of mouse embryonic fibroblasts (MEFs) and human foreskin fibroblasts (hFFs) on the growth of human embryonic stem cells (hESCs). In addition, the secretion levels of basic fibroblast growth factor (bFGF) by the feeder layers was detected. MEFs and hFFs were treated with mitomycin C and seeded onto gelatin-coated plates at a density of 1x108 cells/l. The hFFs and MEFs were combined and plated at the following ratios: 0:1, 1:2, 1:1, 2:1 and 1:0. The secretion of bFGF by the various hFF/MEF ratio feeder layers was detected using an enzyme-linked immunosorbent assay. Subsequently, hESCs were cultured on top of the various feeder layers. The differences in the cellular morphology of the hESCs were observed using microscopy, and the expression levels alkaline phosphatase (AKP) and octamer-binding transcription factor 4 (OCT-4) were detected using immunohistochemical analysis as indicators of differentiation status. The results showed that the hFFs secreted substantial quantities of bFGF, while no bFGF was secreted by the MEFs. The clones of hESC growing on the feeder layer containing MEF or hFF alone were flat. By contrast, hESC clones grown on a mixed feeder layer containing hFFs + MEFs at a ratio of 1:1 exhibited an accumulated growth with a clear edge, as compared with the other ratios. In addition, hESCs growing on the feeder layer were positive for the expression of AKP and OCT-4. In summary, feeder layer hFFs secreted bFGF, while MEFs did not, indicating that bFGF is not the only factor that supports the growth and differentiation of hESCs. The optimal growth of hESCs was achieved using a mixed feeder layer composed of hFFs + MEFs at a ratio of 1:1. © 2016, Spandidos Publications. All rights reserved. Source

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