Identification of baseline gene expression signatures predicting therapeutic responses to three biologic agents in rheumatoid arthritis: a retrospective observational study

Ranked gene list by GSEA (TCZ analysis). (XLSX 984 kb

Increasing Colonoscopy Compliance Using a Blood-Based Risk Assessment Test for Colorectal Cancer

ColonSentry® is a minimally invasive, blood-based risk assessment test for colorectal cancer. The test is used to increase patient compliance with colonoscopy. Many physicians have inquired about the incidence of non-malignant lesions found in patients after colonoscopy prompted by an increased risk score on the ColonSentry test. Here we report on the colonoscopy results of five patients with increased ColonSentry risk scores. Of those five patients, three were determined to have polyps, one of which was pre-malignant

Blood-Based Biomarkers of Aggressive Prostate Cancer

Purpose: Prostate cancer is a bimodal disease with aggressive and indolent forms. Current prostate-specific-antigen testing and digital rectal examination screening provide ambiguous results leading to both under-and over-treatment. Accurate, consistent diagnosis is crucial to risk-stratify patients and facilitate clinical decision making as to treatment versus active surveillance. Diagnosis is currently achieved by needle biopsy, a painful procedure. Thus, there is a clinical need for a minimally-invasive test to determine prostate cancer aggressiveness. A blood sample to predict Gleason score, which is known to reflect aggressiveness of the cancer, could serve as such a test. Materials and Methods: Blood mRNA was isolated from North American and Malaysian prostate cancer patients/controls. Microarray analysis was conducted utilizing the Affymetrix U133 plus 2·0 platform. Expression profiles from 255 patients/controls generated 85 candidate biomarkers. Following quantitative real-time PCR (qRT-PCR) analysis, ten disease-associated biomarkers remained for paired statistical analysis and normalization. Results: Microarray analysis was conducted to identify 85 genes differentially expressed between aggressive prostate cancer (Gleason score ≥8) and controls. Expression of these genes was qRT-PCR verified. Statistical analysis yielded a final seven-gene panel evaluated as six gene-ratio duplexes. This molecular signature predicted as aggressive (ie, Gleason score ≥8) 55% of G6 samples, 49% of G7(3+4), 79% of G7(4+3) and 83% of G8-10, while rejecting 98% of controls. Conclusion: In this study, we have developed a novel, blood-based biomarker panel which can be used as the basis of a simple blood test to identify men with aggressive prostate cancer and thereby reduce the overdiagnosis and overtreatment that currently results from diagnosis using PSA alone. We discuss possible clinical uses of the panel to identify men more likely to benefit from biopsy and immediate therapy versus those more suited to an “active surveillance” strategy

Novel intronic microRNA represses zebrafish myf5 promoter activity through silencing dickkopf-3 gene

A strong, negative cis-element located at the first intron +502/+835 (I300) of zebrafish myf5 has been reported. To elucidate the molecular mechanism underlying this repression network, we microinjected zebrafish single-cell embryos with I300 RNA, resulting in the dramatic reduction of luciferase activity driven by the myf5 promoter. Within this I300 segment, we identified an intronic microRNA (miR-In300) located at +609/+632 and found that it was more highly expressed in the older mature somites than those newly formed, which negatively correlated with the distribution of zebrafish myf5 transcripts. We proved that miR-In300 suppressed the transcription of myf5 through abolishing myf5 promoter activity, and we subsequently identified the long isoform of the Dickkopf-3 gene (dkk3) as the target gene of miR-In300. We further found that injection of the dkk3-morpholinos (MOs) resulted in downregulation of myf5 transcripts in somites, whereas co-injection of myf5 mRNA with dkk3-MO1 enabled rescue of the defects induced by dkk3-MO1 alone. Finally, injection of miR-In300-MO enhanced both myf5 transcripts in somites and the level of Dkk3 protein in zebrafish embryos. Based on these findings, we concluded that miR-In300 binds to its target gene dkk3, which inhibits the translation of dkk3 mRNA and, in turn, suppresses zebrafish myf5 promoter activity

Venice Chart International Consensus Document on Atrial Fibrillation Ablation: 2011 Update

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93647/1/j.1540-8167.2012.02381.x.pd

Off-line evaluation of indoor positioning systems in different scenarios: the experiences from IPIN 2020 competition

Every year, for ten years now, the IPIN competition has aimed at evaluating real-world indoor localisation systems by testing them in a realistic environment, with realistic movement, using the EvAAL framework. The competition provided a unique overview of the state-of-the-art of systems, technologies, and methods for indoor positioning and navigation purposes. Through fair comparison of the performance achieved by each system, the competition was able to identify the most promising approaches and to pinpoint the most critical working conditions. In 2020, the competition included 5 diverse off-site off-site Tracks, each resembling real use cases and challenges for indoor positioning. The results in terms of participation and accuracy of the proposed systems have been encouraging. The best performing competitors obtained a third quartile of error of 1 m for the Smartphone Track and 0.5 m for the Foot-mounted IMU Track. While not running on physical systems, but only as algorithms, these results represent impressive achievements.Track 3 organizers were supported by the European Union’s Horizon 2020 Research and Innovation programme under the Marie Skłodowska Curie Grant 813278 (A-WEAR: A network for dynamic WEarable Applications with pRivacy constraints), MICROCEBUS (MICINN, ref. RTI2018-095168-B-C55, MCIU/AEI/FEDER UE), INSIGNIA (MICINN ref. PTQ2018-009981), and REPNIN+ (MICINN, ref. TEC2017-90808-REDT). We would like to thanks the UJI’s Library managers and employees for their support while collecting the required datasets for Track 3. Track 5 organizers were supported by JST-OPERA Program, Japan, under Grant JPMJOP1612. Track 7 organizers were supported by the Bavarian Ministry for Economic Affairs, Infrastructure, Transport and Technology through the Center for Analytics-Data-Applications (ADA-Center) within the framework of “BAYERN DIGITAL II. ” Team UMinho (Track 3) was supported by FCT—Fundação para a Ciência e Tecnologia within the R&D Units Project Scope under Grant UIDB/00319/2020, and the Ph.D. Fellowship under Grant PD/BD/137401/2018. Team YAI (Track 3) was supported by the Ministry of Science and Technology (MOST) of Taiwan under Grant MOST 109-2221-E-197-026. Team Indora (Track 3) was supported in part by the Slovak Grant Agency, Ministry of Education and Academy of Science, Slovakia, under Grant 1/0177/21, and in part by the Slovak Research and Development Agency under Contract APVV-15-0091. Team TJU (Track 3) was supported in part by the National Natural Science Foundation of China under Grant 61771338 and in part by the Tianjin Research Funding under Grant 18ZXRHSY00190. Team Next-Newbie Reckoners (Track 3) were supported by the Singapore Government through the Industry Alignment Fund—Industry Collaboration Projects Grant. This research was conducted at Singtel Cognitive and Artificial Intelligence Lab for Enterprises (SCALE@NTU), which is a collaboration between Singapore Telecommunications Limited (Singtel) and Nanyang Technological University (NTU). Team KawaguchiLab (Track 5) was supported by JSPS KAKENHI under Grant JP17H01762. Team WHU&AutoNavi (Track 6) was supported by the National Key Research and Development Program of China under Grant 2016YFB0502202. Team YAI (Tracks 6 and 7) was supported by the Ministry of Science and Technology (MOST) of Taiwan under Grant MOST 110-2634-F-155-001

Real-world Effectiveness and Tolerability of Interferon-free Direct-acting Antiviral for 15,849 Patients with Chronic Hepatitis C: A Multinational Cohort Study

BACKGROUND AND AIMS: As practice patterns and hepatitis C virus (HCV) genotypes (GT) vary geographically, a global real-world study from both East and West covering all GTs can help inform practice policy toward the 2030 HCV elimination goal. This study aimed to assess the effectiveness and tolerability of DAA treatment in routine clinical practice in a multinational cohort for patients infected with all HCV GTs, focusing on GT3 and GT6. METHODS: We analyzed the sustained virological response (SVR12) of 15,849 chronic hepatitis C patients from 39 Real-World Evidence from the Asia Liver Consortium for HCV clinical sites in Asia Pacific, North America, and Europe between 07/01/2014-07/01/2021. RESULTS: The mean age was 62±13 years, with 49.6% male. The demographic breakdown was 91.1% Asian (52.9% Japanese, 25.7% Chinese/Taiwanese, 5.4% Korean, 3.3% Malaysian, and 2.9% Vietnamese), 6.4% White, 1.3% Hispanic/Latino, and 1% Black/African-American. Additionally, 34.8% had cirrhosis, 8.6% had hepatocellular carcinoma (HCC), and 24.9% were treatment-experienced (20.7% with interferon, 4.3% with direct-acting antivirals). The largest group was GT1 (10,246 [64.6%]), followed by GT2 (3,686 [23.2%]), GT3 (1,151 [7.2%]), GT6 (457 [2.8%]), GT4 (47 [0.3%]), GT5 (1 [0.006%]), and untyped GTs (261 [1.6%]). The overall SVR12 was 96.9%, with rates over 95% for GT1/2/3/6 but 91.5% for GT4. SVR12 for GT3 was 95.1% overall, 98.2% for GT3a, and 94.0% for GT3b. SVR12 was 98.3% overall for GT6, lower for patients with cirrhosis and treatment-experienced (TE) (93.8%) but ≥97.5% for treatment-naive patients regardless of cirrhosis status. On multivariable analysis, advanced age, prior treatment failure, cirrhosis, active HCC, and GT3/4 were independent predictors of lower SVR12, while being Asian was a significant predictor of achieving SVR12. CONCLUSIONS: In this diverse multinational real-world cohort of patients with various GTs, the overall cure rate was 96.9%, despite large numbers of patients with cirrhosis, HCC, TE, and GT3/6. SVR12 for GT3/6 with cirrhosis and TE was lower but still excellent (\u3e91%)

2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

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Degradation aspects of water formation and transport in Proton Exchange Membrane Fuel Cell: A review

This review paper summarises the key aspects of Proton Exchange Membrane Fuel Cell (PEMFC) degradation that are associated with water formation, retention, accumulation, and transport mechanisms within the cell. Issues related to loss of active surface area of the catalyst, ionomer dissolution, membrane swelling, ice formation, corrosion, and contamination are also addressed and discussed. The impact of each of these water mechanisms on cell performance and durability was found to be different and to vary according to the design of the cell and its operating conditions. For example, the presence of liquid water within Membrane Electrode Assembly (MEA), as a result of water accumulation, can be detrimental if the operating temperature of the cell drops to sub-freezing. The volume expansion of liquid water due to ice formation can damage the morphology of different parts of the cell and may shorten its life-time. This can be more serious, for example, during the water transport mechanism where migration of Pt particles from the catalyst may take place after detachment from the carbon support. Furthermore, the effect of transport mechanism could be augmented if humid reactant gases containing impurities poison the membrane, leading to the same outcome as water retention or accumulation. Overall, the impact of water mechanisms can be classified as aging or catastrophic. Aging has a long-term impact over the duration of the PEMFC life-time whereas in the catastrophic mechanism the impact is immediate. The conversion of cell residual water into ice at sub-freezing temperatures by the water retention/ accumulation mechanism and the access of poisoning contaminants through the water transport mechanism are considered to fall into the catastrophic category. The effect of water mechanisms on PEMFC degradation can be reduced or even eliminated by (a) using advanced materials for improving the electrical, chemical and mechanical stability of the cell components against deterioration, and (b) implementing effective strategies for water management in the cell

2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

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