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  1. Shi W, Massaia A, Louzada S, Banerjee R, Hallast P, Chen Y, et al.
    Hum. Genet., 2018 Jan;137(1):73-83.
    PMID: 29209947 DOI: 10.1007/s00439-017-1857-9
    We describe the variation in copy number of a ~ 10 kb region overlapping the long intergenic noncoding RNA (lincRNA) gene, TTTY22, within the IR3 inverted repeat on the short arm of the human Y chromosome, leading to individuals with 0-3 copies of this region in the general population. Variation of this CNV is common, with 266 individuals having 0 copies, 943 (including the reference sequence) having 1, 23 having 2 copies, and two having 3 copies, and was validated by breakpoint PCR, fibre-FISH, and 10× Genomics Chromium linked-read sequencing in subsets of 1234 individuals from the 1000 Genomes Project. Mapping the changes in copy number to the phylogeny of these Y chromosomes previously established by the Project identified at least 20 mutational events, and investigation of flanking paralogous sequence variants showed that the mutations involved flanking sequences in 18 of these, and could extend over > 30 kb of DNA. While either gene conversion or double crossover between misaligned sister chromatids could formally explain the 0-2 copy events, gene conversion is the more likely mechanism, and these events include the longest non-allelic gene conversion reported thus far. Chromosomes with three copies of this CNV have arisen just once in our data set via another mechanism: duplication of 420 kb that places the third copy 230 kb proximal to the existing proximal copy. Our results establish gene conversion as a previously under-appreciated mechanism of generating copy number changes in humans and reveal the exceptionally large size of the conversion events that can occur.
  2. Chiu PW, Sano Y, Uedo N, Singh R, Ng EKW, Aang TL, et al.
    Endosc Int Open, 2019 Apr;7(4):E452-E458.
    PMID: 30931377 DOI: 10.1055/a-0854-3525
    Background and study aims  Image enhanced endoscopy (IEE) allows endoscopists to improve recognition and characterization of gastrointestinal neoplasia. The Asian Novel Bio-Imaging and Intervention Group (ANBIG) conducted a standardized training program in endoscopic diagnosis and treatment of early gastrointestinal cancers in Asia. We embarked on a study to investigate the effect of this module on endoscopic diagnosis of early gastrointestinal neoplasia. Methods  This prospectively collected database was from workshops conducted on training for endoscopic diagnosis of early gastrointestinal neoplasia. All workshops were conducted in a standardized format, which included a pretest, a learning phase consisting of didactic lectures, case discussion, and live demonstration followed by a post-test to assess knowledge gained. The pretest and post-training tests were standardized questions addressing four domains, including basic knowledge of imaging and diagnosis of esophageal, gastric, and colonic neoplasia. Results  From November 2013 to November 2016, 41 ANBIG workshops were conducted in 13 countries. A total of 1863 delegates and 40 faculty participated in these workshops. Of the delegates, 627 completed both tests. There was a significant improvement after training in all domains of the tests. There was a trend in general lack of knowledge across all domains for delegates from "low" healthcare cost countries before training. All delegates demonstrated significant improvement in knowledge of all domains after the workshop irrespective of whether they were from "high" or "low" healthcare cost per capita countries. Conclusion  A standardized teaching program on IEE improved the diagnostic ability and quality of endoscopists in recognizing early gastrointestinal neoplasia in Asia.
  3. Mahmod M, Pal N, Rayner J, Holloway C, Raman B, Dass S, et al.
    J Cardiovasc Magn Reson, 2018 12 24;20(1):88.
    PMID: 30580760 DOI: 10.1186/s12968-018-0511-6
    BACKGROUND: Heart failure (HF) is characterized by altered myocardial substrate metabolism which can lead to myocardial triglyceride accumulation (steatosis) and lipotoxicity. However its role in mild HF with preserved ejection fraction (HFpEF) is uncertain. We measured myocardial triglyceride content (MTG) in HFpEF and assessed its relationships with diastolic function and exercise capacity.

    METHODS: Twenty seven HFpEF (clinical features of HF, left ventricular EF >50%, evidence of mild diastolic dysfunction and evidence of exercise limitation as assessed by cardiopulmonary exercise test) and 14 controls underwent 1H-cardiovascular magnetic resonance spectroscopy (1H-CMRS) to measure MTG (lipid/water, %), 31P-CMRS to measure myocardial energetics (phosphocreatine-to-adenosine triphosphate - PCr/ATP) and feature-tracking cardiovascular magnetic resonance (CMR) imaging for diastolic strain rate.

    RESULTS: When compared to controls, HFpEF had 2.3 fold higher in MTG (1.45 ± 0.25% vs. 0.64 ± 0.16%, p = 0.009) and reduced PCr/ATP (1.60 ± 0.09 vs. 2.00 ± 0.10, p = 0.005). HFpEF had significantly reduced diastolic strain rate and maximal oxygen consumption (VO2 max), which both correlated significantly with elevated MTG and reduced PCr/ATP. On multivariate analyses, MTG was independently associated with diastolic strain rate while diastolic strain rate was independently associated with VO2 max.

    CONCLUSIONS: Myocardial steatosis is pronounced in mild HFpEF, and is independently associated with impaired diastolic strain rate which is itself related to exercise capacity. Steatosis may adversely affect exercise capacity by indirect effect occurring via impairment in diastolic function. As such, myocardial triglyceride may become a potential therapeutic target to treat the increasing number of patients with HFpEF.

  4. Singh R, Jayanna M, Wong J, Lim LG, Zhang J, Lv J, et al.
    Endosc Int Open, 2015 Feb;3(1):E14-8.
    PMID: 26134765 DOI: 10.1055/s-0034-1377610
    The advent and utility of new endoscopic imaging modalities for predicting the histology of Barrett's esophagus (BE) in real time with high accuracy appear promising and could potentially obviate the need to perform random biopsies where guidelines are poorly adhered to. We embarked on evaluating the performance characteristics of white-light endoscopy with magnification (WLE-z), narrow-band imaging with magnification (NBI-z) and a combination of both modalities.
  5. Park DI, Hisamatsu T, Chen M, Ng SC, Ooi CJ, Wei SC, et al.
    Intest Res, 2018 Jan;16(1):17-25.
    PMID: 29422794 DOI: 10.5217/ir.2018.16.1.17
    Because anti-tumor necrosis factor (anti-TNF) therapy has become increasingly popular in many Asian countries, the risk of developing active tuberculosis (TB) among anti-TNF users may raise serious health problems in this region. Thus, the Asian Organization for Crohn's and Colitis and the Asia Pacific Association of Gastroenterology have developed a set of consensus statements about risk assessment, detection and prevention of latent TB infection, and management of active TB infection in patients with inflammatory bowel disease (IBD) receiving anti-TNF treatment. Twenty-three consensus statements were initially drafted and then discussed by the committee members. The quality of evidence and the strength of recommendations were assessed by using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Web-based consensus voting was performed by 211 IBD specialists from 9 Asian countries concerning each statement. A consensus statement was accepted if at least 75% of the participants agreed. Part 2 of the statements comprised 3 parts: management of latent TB in preparation for anti-TNF therapy, monitoring during anti-TNF therapy, and management of an active TB infection after anti-TNF therapy. These consensus statements will help clinicians optimize patient outcomes by reducing the morbidity and mortality related to TB infections in patients with IBD receiving anti-TNF treatment.
  6. Park DI, Hisamatsu T, Chen M, Ng SC, Ooi CJ, Wei SC, et al.
    J. Gastroenterol. Hepatol., 2018 Jan;33(1):20-29.
    PMID: 29023903 DOI: 10.1111/jgh.14019
    Because anti-tumor necrosis factor (anti-TNF) therapy has become increasingly popular in many Asian countries, the risk of developing active tuberculosis (TB) among anti-TNF users may raise serious health problems in this region. Thus, the Asian Organization for Crohn's and Colitis and the Asian Pacific Association of Gastroenterology have developed a set of consensus statements about risk assessment, detection, and prevention of latent TB infection and management of active TB infection in patients with inflammatory bowel disease (IBD) receiving anti-TNF treatment. Twenty-three consensus statements were initially drafted and then discussed by the committee members. The quality of evidence and the strength of recommendations were assessed by using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Web-based consensus voting was performed by 211 IBD specialists from nine Asian countries concerning each statement. A consensus statement was accepted if at least 75% of the participants agreed. Part 1 of the statements comprised two parts: (i) risk of TB infection during anti-TNF therapy and (ii) screening for TB infection prior to commencing anti-TNF therapy. These consensus statements will help clinicians optimize patient outcomes by reducing the morbidity and mortality related to TB infections in patients with IBD receiving anti-TNF treatment.
  7. Park DI, Hisamatsu T, Chen M, Ng SC, Ooi CJ, Wei SC, et al.
    Intest Res, 2018 Jan;16(1):4-16.
    PMID: 29422793 DOI: 10.5217/ir.2018.16.1.4
    Because anti-tumor necrosis factor (anti-TNF) therapy has become increasingly popular in many Asian countries, the risk of developing active tuberculosis (TB) among anti-TNF users may raise serious health problems in this region. Thus, the Asian Organization for Crohn's and Colitis and the Asia Pacific Association of Gastroenterology have developed a set of consensus statements about risk assessment, detection and prevention of latent TB infection, and management of active TB infection in patients with inflammatory bowel disease (IBD) receiving anti-TNF treatment. Twenty-three consensus statements were initially drafted and then discussed by the committee members. The quality of evidence and the strength of recommendations were assessed by using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Web-based consensus voting was performed by 211 IBD specialists from 9 Asian countries concerning each statement. A consensus statement was accepted if at least 75% of the participants agreed. Part 1 of the statements comprised 2 parts: risk of TB infection Recommendaduring anti-TNF therapy, and screening for TB infection prior to commencing anti-TNF therapy. These consensus statements will help clinicians optimize patient outcomes by reducing the morbidity and mortality related to TB infections in patients with IBD receiving anti-TNF treatment.
  8. Park DI, Hisamatsu T, Chen M, Ng SC, Ooi CJ, Wei SC, et al.
    J. Gastroenterol. Hepatol., 2018 Jan;33(1):30-36.
    PMID: 29024102 DOI: 10.1111/jgh.14018
    Because anti-tumor necrosis factor (anti-TNF) therapy has become increasingly popular in many Asian countries, the risk of developing active tuberculosis (TB) among anti-TNF users may raise serious health problems in this region. Thus, the Asian Organization for Crohn's and Colitis and the Asia Pacific Association of Gastroenterology have developed a set of consensus statements about risk assessment, detection and prevention of latent TB infection, and management of active TB infection in patients with inflammatory bowel disease (IBD) receiving anti-TNF treatment. Twenty-three consensus statements were initially drafted and then discussed by the committee members. The quality of evidence and the strength of recommendations were assessed by using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Web-based consensus voting was performed by 211 IBD specialists from nine Asian countries concerning each statement. A consensus statement was accepted if at least 75% of the participants agreed. Part 2 of the statements comprised three parts: (3) management of latent TB in preparation for anti-TNF therapy, (4) monitoring during anti-TNF therapy, and (5) management of an active TB infection after anti-TNF therapy. These consensus statements will help clinicians optimize patient outcomes by reducing the morbidity and mortality related to TB infections in patients with IBD receiving anti-TNF treatment.
  9. Yao K, Uedo N, Muto M, Ishikawa H, Cardona HJ, Filho ECC, et al.
    EBioMedicine, 2016 Jul;9:140-147.
    PMID: 27333048 DOI: 10.1016/j.ebiom.2016.05.016
    BACKGROUND: In many countries, gastric cancer is not diagnosed until an advanced stage. An Internet-based e-learning system to improve the ability of endoscopists to diagnose gastric cancer at an early stage was developed and was evaluated for its effectiveness.

    METHODS: The study was designed as a randomized controlled trial. After receiving a pre-test, participants were randomly allocated to either an e-learning or non-e-learning group. Only those in the e-learning group gained access to the e-learning system. Two months after the pre-test, both groups received a post-test. The primary endpoint was the difference between the two groups regarding the rate of improvement of their test results.

    FINDINGS: 515 endoscopists from 35 countries were assessed for eligibility, and 332 were enrolled in the study, with 166 allocated to each group. Of these, 151 participants in the e-learning group and 144 in the non-e-learning group were included in the analysis. The mean improvement rate (standard deviation) in the e-learning and non-e-learning groups was 1·24 (0·26) and 1·00 (0·16), respectively (P<0·001).

    INTERPRETATION: This global study clearly demonstrated the efficacy of an e-learning system to expand knowledge and provide invaluable experience regarding the endoscopic detection of early gastric cancer (R000012039).

  10. Ooi CJ, Hilmi I, Banerjee R, Chuah SW, Ng SC, Wei SC, et al.
    PMID: 30848854 DOI: 10.1111/jgh.14648
    The Asia-Pacific Working Group on Inflammatory Bowel Disease was established in Cebu, Philippines, under the auspices of the Asia-Pacific Association of Gastroenterology with the goal of improving inflammatory bowel disease care in Asia. This consensus is carried out in collaboration with Asian Organization for Crohn's and Colitis. With biologic agents and biosimilars becoming more established, it is necessary to conduct a review on existing literature and establish a consensus on when and how to introduce biologic agents and biosimilars in conjunction with conventional treatments for ulcerative colitis and Crohn's disease in Asia. These statements also address how pharmacogenetics influences the treatments of ulcerative colitis and Crohn's disease and provides guidance on response monitoring and strategies to restore loss of response. Finally, the review includes statements on how to manage treatment alongside possible hepatitis B and tuberculosis infections, both common in Asia. These statements have been prepared and voted upon by members of inflammatory bowel disease workgroup employing the modified Delphi process. These statements do not intend to be all-encompassing, and future revisions are likely as new data continue to emerge.
  11. Ooi CJ, Hilmi I, Banerjee R, Chuah SW, Ng SC, Wei SC, et al.
    Intest Res, 2019 Jul;17(3):285-310.
    PMID: 31146509 DOI: 10.5217/ir.2019.00026
    The Asia-Pacific Working Group on inflammatory bowel disease (IBD) was established in Cebu, Philippines, under the auspices of the Asian Pacific Association of Gastroenterology with the goal of improving IBD care in Asia. This consensus is carried out in collaboration with Asian Organization for Crohn's and Colitis. With biologic agents and biosimilars becoming more established, it is necessary to conduct a review on existing literature and establish a consensus on when and how to introduce biologic agents and biosimilars in the conjunction with conventional treatments for ulcerative colitis (UC) and Crohn's disease (CD) in Asia. These statements also address how pharmacogenetics influence the treatments of UC and CD and provide guidance on response monitoring and strategies to restore loss of response. Finally, the review includes statements on how to manage treatment alongside possible hepatitis B and tuberculosis infections, both common in Asia. These statements have been prepared and voted upon by members of IBD workgroup employing the modified Delphi process. These statements do not intend to be all-encompassing and future revisions are likely as new data continue to emerge.
  12. Ng SC, Kaplan GG, Tang W, Banerjee R, Adigopula B, Underwood FE, et al.
    Am. J. Gastroenterol., 2019 Jan;114(1):107-115.
    PMID: 30177785 DOI: 10.1038/s41395-018-0233-2
    INTRODUCTION: Living in an urban environment may increase the risk of developing inflammatory bowel disease (IBD). It is unclear if this observation is seen globally. We conducted a population-based study to assess the relationship between urbanization and incidence of IBD in the Asia-Pacific region.

    METHODS: Newly diagnosed IBD cases between 2011 and 2013 from 13 countries or regions in Asia-Pacific were included. Incidence was calculated with 95% confidence interval (CI) and pooled using random-effects model. Meta-regression analysis was used to assess incidence rates and their association with population density, latitude, and longitude.

    RESULTS: We identified 1175 ulcerative colitis (UC), 656 Crohn's disease (CD), and 37 IBD undetermined (IBD-U). Mean annual IBD incidence per 100 000 was 1.50 (95% CI: 1.43-1.57). India (9.31; 95% CI: 8.38-10.31) and China (3.64; 95% CI, 2.97-4.42) had the highest IBD incidence in Asia. Incidence of overall IBD (incidence rate ratio [IRR]: 2.19; 95% CI: 1.01-4.76]) and CD (IRR: 3.28; 95% CI: 1.83-9.12) was higher across 19 areas of Asia with a higher population density. In China, incidence of IBD (IRR: 2.37; 95% CI: 1.10-5.16) and UC (IRR: 2.63; 95% CI: 1.2-5.8) was positively associated with gross domestic product. A south-to-north disease gradient (IRR: 0.94; 95% CI: 0.91-0.98) was observed for IBD incidence and a west-to-east gradient (IRR: 1.14; 95% CI: 1.05-1.24) was observed for CD incidence in China. This study received IRB approval.

    CONCLUSIONS: Regions in Asia with a high population density had a higher CD and UC incidence. Coastal areas within China had higher IBD incidence. With increasing urbanization and a shift from rural areas to cities, disease incidence may continue to climb in Asia.

  13. Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Acevedo Arozena A, et al.
    Autophagy, 2016;12(1):1-222.
    PMID: 26799652 DOI: 10.1080/15548627.2015.1100356
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