2,201 research outputs found

    Coarse-to-Fine Annotation Enrichment for Semantic Segmentation Learning

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    Rich high-quality annotated data is critical for semantic segmentation learning, yet acquiring dense and pixel-wise ground-truth is both labor- and time-consuming. Coarse annotations (e.g., scribbles, coarse polygons) offer an economical alternative, with which training phase could hardly generate satisfactory performance unfortunately. In order to generate high-quality annotated data with a low time cost for accurate segmentation, in this paper, we propose a novel annotation enrichment strategy, which expands existing coarse annotations of training data to a finer scale. Extensive experiments on the Cityscapes and PASCAL VOC 2012 benchmarks have shown that the neural networks trained with the enriched annotations from our framework yield a significant improvement over that trained with the original coarse labels. It is highly competitive to the performance obtained by using human annotated dense annotations. The proposed method also outperforms among other state-of-the-art weakly-supervised segmentation methods.Comment: CIKM 2018 International Conference on Information and Knowledge Managemen

    Phosphorylation of the Human La Antigen on Serine 366 Can Regulate Recycling of RNA Polymerase III Transcription Complexes

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    AbstractThe human La antigen is an RNA-binding protein that facilitates transcriptional termination and reinitiation by RNA polymerase III. Native La protein fractionates into transcriptionally active and inactive forms that are unphosphorylated and phosphorylated at serine 366, respectively, as determined by enzymatic and mass spectrometric analyses. Serine 366 comprises a casein kinase II phosphorylation site that resides within a conserved region in the La proteins from several species. RNA synthesis from isolated transcription complexes is inhibited by casein kinase II-mediated phosphorylation of La serine 366 and is reversible by dephosphorylation. This work demonstrates a novel mechanism of transcriptional control at the level of recycling of stable transcription complexes

    Placebo devices as effective control methods in acupuncture clinical trials : a systematic review

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    While the use of acupuncture has been recognised by the World Health Organisation, its efficacy for many of the common clinical conditions is still undergoing validation through randomised controlled trials (RCTs). A credible placebo control for such RCTs to enable meaningful evaluation of its efficacy is to be established. While several non-penetrating acupuncture placebo devices, namely the Streitberger, the Park and the Takakura Devices, have been developed and used in RCTs, their suitability as inert placebo controls needs to be rigorously determined. This article systematically reviews these devices as placebo interventions. Electronic searches were conducted on four English and two Chinese databases from their inceptions to July 2014; hand searches of relevant references were also conducted. RCTs, in English or Chinese language, comparing acupuncture with one of the aforementioned devices as the control intervention on human participants with any clinical condition and evaluating clinically related outcomes were included. Thirty-six studies were included for qualitative analysis while 14 were in the meta-analysis. The meta-analysis does not support the notion of either the Streitberger or the Park Device being inert control interventions while none of the studies involving the Takakura Device was included in the meta-analysis. Sixteen studies reported the occurrence of adverse events, with no significant difference between verum and placebo acupuncture. Author-reported blinding credibility showed that participant blinding was successful in most cases; however, when blinding index was calculated, only one study, which utilised the Park Device, seemed to have an ideal blinding scenario. Although the blinding index could not be calculated for the Takakura Device, it was the only device reported to enable practitioner blinding. There are limitations with each of the placebo devices and more rigorous studies are needed to further evaluate their effects and blinding credibility

    Cranberry Polyphenols in Esophageal Cancer Inhibition: New Insights

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    Esophageal adenocarcinoma (EAC) is a cancer characterized by rapidly rising incidence and poor survival, resulting in the need for new prevention and treatment options. We utilized two cranberry polyphenol extracts, one proanthocyanidin enriched (C-PAC) and a combination of anthocyanins, flavonoids, and glycosides (AFG) to assess inhibitory mechanisms utilizing premalignant Barrett’s esophagus (BE) and EAC derived cell lines. We employed reverse phase protein arrays (RPPA) and Western blots to examine cancer-associated pathways and specific signaling cascades modulated by C-PAC or AFG. Viability results show that C-PAC is more potent than AFG at inducing cell death in BE and EAC cell lines. Based on the RPPA results, C-PAC significantly modulated 37 and 69 proteins in JH-EsoAd1 (JHAD1) and OE19 EAC cells, respectively. AFG treatment significantly altered 49 proteins in both JHAD1 and OE19 cells. Bioinformatic analysis of RPPA results revealed many previously unidentified pathways as modulated by cranberry polyphenols including NOTCH signaling, immune response, and epithelial to mesenchymal transition. Collectively, these results provide new insight regarding mechanisms by which cranberry polyphenols exert cancer inhibitory effects targeting EAC, with implications for potential use of cranberry constituents as cancer preventive agents

    The long noncoding RNA, treRNA, decreases DNA damage and is associated with poor response to chemotherapy in chronic lymphocytic leukemia.

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    The study of long noncoding RNAs (lncRNAs) is an emerging area of cancer research, in part due to their ability to serve as disease biomarkers. However, few studies have investigated lncRNAs in chronic lymphocytic leukemia (CLL). We have identified one particular lncRNA, treRNA, which is overexpressed in CLL B-cells. We measured transcript expression in 144 CLL patient samples and separated samples into high or low expression of treRNA relative to the overall median. We found that high expression of treRNA is significantly associated with shorter time to treatment. High treRNA also correlates with poor prognostic indicators such as unmutated IGHV and high ZAP70 protein expression. We validated these initial findings in samples collected in a clinical trial comparing the nucleoside analog fludarabine alone or in combination with the alkylating agent cyclophosphamide in untreated CLL samples collected prior to starting therapy (E2997). High expression of treRNA was independently prognostic for shorter progression free survival in patients receiving fludarabine plus cyclophosphamide. Given these results, in order to study the role of treRNA in DNA damage response we generated a model cell line system where treRNA was over-expressed in the human B-CLL cell line OSU-CLL. Relative to the vector control line, there was less cell death in OSU-CLL over-expressing treRNA after exposure to fludarabine and mafosfamide, due in part to a reduction in DNA damage. Therefore, we suggest that treRNA is a novel biomarker in CLL associated with aggressive disease and poor response to chemotherapy through enhanced protection against cytotoxic mediated DNA damage

    Effect of subcutaneous methylnaltrexone on patient-reported constipation symptoms

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    AbstractBackgroundMethylnaltrexone, a selective peripheral acting mu-opioid receptor antagonist, alleviates the constipating effects of opioids without affecting centrally mediated analgesia.ObjectivesTo assess the effect of subcutaneous (SC) methylnaltrexone injection on patient-reported constipation symptoms and pain scores.MethodsA total of 469 subjects on opioids for chronic non-malignant pain with opioid-induced constipation were randomized to methylnaltrexone SC with once daily (QD) or every other day (QOD) dosing or placebo for 4 weeks. Constipation symptoms and pain were assessed using the patient assessment of constipation–symptoms (PAC-SYM) questionnaire and a 11-point scale, respectively, at baseline, Day 14 and Day 28. Change from baseline in PAC-SYM and pain scores were compared between methylnaltrexone and placebo arms at Day 28 using analysis of covariance, with treatment group as factor and baseline score as covariate.ResultsA majority of patients were women (60%), average age was 49 years old, and back pain (60%) was the primary pain condition. At Day 28, the methylnaltrexone SC QD group showed a significant improvement over placebo for rectal symptoms (−0.56 vs. –0.30; P < 0.05), stool symptoms (−0.76 vs. –0.43; P < 0.001) and global scores (−0.62 vs. –0.37; P < 0.001). Improvement in stool symptoms (−0.69 vs.−0.43; P < 0.05) and the global scores (−0.52 vs. –0.37; P < 0.05) were significantly greater than placebo in the methylnaltrexone QOD group. Differences in change from baseline in abdominal symptoms and pain scores between the methylnaltrexone SC QD or QOD dosing arms and placebo were not significant.ConclusionThe results of our study indicate significant improvement in constipation symptoms with methylnaltrexone QD or QOD dosing compared to placebo without a significant effect on pain scores

    Initial uptake, time to treatment, and real-world effectiveness of all-oral direct-acting antivirals for hepatitis C virus infection in the United States: A retrospective cohort analysis

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    BACKGROUND: Data on initiation and utilization of direct-acting antiviral therapies for hepatitis C virus infection in the United States are limited. This study evaluated treatment initiation, time to treatment, and real-world effectiveness of direct-acting antiviral therapy in individuals with hepatitis C virus infection treated during the first 2 years of availability of all-oral direct-acting antiviral therapies. METHODS: A retrospective cohort analysis was undertaken using electronic medical records and chart review abstraction of hepatitis C virus-infected individuals aged >18 years diagnosed with chronic hepatitis C virus infection between January 1, 2014, and December 31, 2015 from the Indiana University Health database. RESULTS: Eight hundred thirty people initiated direct-acting antiviral therapy during the 2-year observation window. The estimated incidence of treatment initiation was 8.8%±0.34% at the end of year 1 and 15.0%±0.5% at the end of year 2. Median time to initiating therapy was 300 days. Using a Cox regression analysis, positive predictors of treatment initiation included age (hazard ratio, 1.008), prior hepatitis C virus treatment (1.74), cirrhosis (2.64), and history of liver transplant (1.5). History of drug abuse (0.43), high baseline alanine aminotransferase levels (0.79), hepatitis B virus infection (0.41), and self-pay (0.39) were negatively associated with treatment initiation. In the evaluable population (n = 423), 83.9% (95% confidence interval, 80.1-87.3%) of people achieved sustained virologic response. CONCLUSION: In the early years of the direct-acting antiviral era, <10% of people diagnosed with chronic hepatitis C virus infection received direct-acting antiviral treatment; median time to treatment initiation was 300 days. Future analyses should evaluate time to treatment initiation among those with less advanced fibrosis

    Stigma never dies: Mourning a spouse who died of AIDS in China

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    Stigma towards people with HIV (PHIV) can affect their family members. In this study of 68 HIV seronegative participants in China whose spouse died of AIDS, 35.3% reported prolonged grief. Stigma beliefs towards PHIV (i.e., belief that PHIV&#39;s death leaves the deceased, the family and society better off) predicted grief symptoms. Social campaigns to combat stigma and grief therapy to reconstruct the meaning of HIV-related death may be helpful to reduce suffering in HIV bereaved. (C) 2015 Elsevier Ireland Ltd. All rights reserved

    Transplantation of Autologous Adipose Stem Cells Lacks Therapeutic Efficacy in the Experimental Autoimmune Encephalomyelitis Model

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    Multiple sclerosis (MS), characterized by chronic inflammation, demyelination, and axonal damage, is a complicated neurological disease of the human central nervous system. Recent interest in adipose stromal/stem cell (ASCs) for the treatment of CNS diseases has promoted further investigation in order to identify the most suitable ASCs. To investigate whether MS affects the biologic properties of ASCs and whether autologous ASCs from MS-affected sources could serve as an effective source for stem cell therapy, cells were isolated from subcutaneous inguinal fat pads of mice with established experimental autoimmune encephalomyelitis (EAE), a murine model of MS. ASCs from EAE mice and their syngeneic wildtype mice were cultured, expanded, and characterized for their cell morphology, surface antigen expression, osteogenic and adipogenic differentiation, colony forming units, and inflammatory cytokine and chemokine levels in vitro. Furthermore, the therapeutic efficacy of the cells was assessed in vivo by transplantation into EAE mice. The results indicated that the ASCs from EAE mice displayed a normal phenotype, typical MSC surface antigen expression, and in vitro osteogenic and adipogenic differentiation capacity, while their osteogenic differentiation capacity was reduced in comparison with their unafflicted control mice. The ASCs from EAE mice also demonstrated increased expression of pro-inflammatory cytokines and chemokines, specifically an elevation in the expression of monocyte chemoattractant protein-1 and keratin chemoattractant. In vivo, infusion of wild type ASCs significantly ameliorate the disease course, autoimmune mediated demyelination and cell infiltration through the regulation of the inflammatory responses, however, mice treated with autologous ASCs showed no therapeutic improvement on the disease progression
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