Message from the ICASE 2011 organizers

published_or_final_versionThe 9th IEEE International Symposium on Parallel and Distributed Processing with Applications Workshops (ISPAW 2011), Busan, Korea, 26-28 May 2011. In Proceedings of the ISPAW, 2011, p. xxx

Implementation of genomics in medical practice to deliver precision medicine for an Asian population

Whilst the underlying principles of precision medicine are comparable across the globe, genomic references, health practices, costs and discrimination policies differ in Asian settings compared to the reported initiatives involving European-derived populations. We have addressed these variables by developing an evolving reference base of genomic and phenotypic data and a framework to return medically significant variants to consenting research participants applicable for the Asian context. Targeting 10,000 participants, over 2000 Singaporeans, with no known pre-existing health conditions, have consented to an extensive clinical health screen, family health history collection, genome sequencing and ongoing follow-up. Genomic variants in a subset of genes associated with Mendelian disorders and drug responses are analysed using an in-house bioinformatics pipeline. A multidisciplinary team reviews the classification of variants and a research report is generated. Medically significant variants are returned to consenting participants through a bespoke return-of-result genomics clinic. Variant validation and subsequent clinical referral are advised as appropriate. The design and implementation of this flexible learning framework enables a cohort of detailed phenotyping and genotyping of healthy Singaporeans to be established and the frequency of disease-causing variants in this population to be determined. Our findings will contribute to international precision medicine initiatives, bridging gaps with ethnic-specific data and insights from this understudied population

Acetylated histone variant H2A.Z is involved in the activation of neo-enhancers in prostate cancer.

Acetylation of the histone variant H2A.Z (H2A.Zac) occurs at active promoters and is associated with oncogene activation in prostate cancer, but its role in enhancer function is still poorly understood. Here we show that H2A.Zac containing nucleosomes are commonly redistributed to neo-enhancers in cancer resulting in a concomitant gain of chromatin accessibility and ectopic gene expression. Notably incorporation of acetylated H2A.Z nucleosomes is a pre-requisite for activation of Androgen receptor (AR) associated enhancers. H2A.Zac nucleosome occupancy is rapidly remodeled to flank the AR sites to initiate the formation of nucleosome-free regions and the production of AR-enhancer RNAs upon androgen treatment. Remarkably higher levels of global H2A.Zac correlate with poorer prognosis. Altogether these data demonstrate the novel contribution of H2A.Zac in activation of newly formed enhancers in prostate cancer

pp32 (ANP32A) Expression Inhibits Pancreatic Cancer Cell Growth and Induces Gemcitabine Resistance by Disrupting HuR Binding to mRNAs

The expression of protein phosphatase 32 (PP32, ANP32A) is low in poorly differentiated pancreatic cancers and is linked to the levels of HuR (ELAV1), a predictive marker for gemcitabine response. In pancreatic cancer cells, exogenous overexpression of pp32 inhibited cell growth, supporting its long-recognized role as a tumor suppressor in pancreatic cancer. In chemotherapeutic sensitivity screening assays, cells overexpressing pp32 were selectively resistant to the nucleoside analogs gemcitabine and cytarabine (ARA-C), but were sensitized to 5-fluorouracil; conversely, silencing pp32 in pancreatic cancer cells enhanced gemcitabine sensitivity. The cytoplasmic levels of pp32 increased after cancer cells are treated with certain stressors, including gemcitabine. pp32 overexpression reduced the association of HuR with the mRNA encoding the gemcitabine-metabolizing enzyme deoxycytidine kinase (dCK), causing a significant reduction in dCK protein levels. Similarly, ectopic pp32 expression caused a reduction in HuR binding of mRNAs encoding tumor-promoting proteins (e.g., VEGF and HuR), while silencing pp32 dramatically enhanced the binding of these mRNA targets. Low pp32 nuclear expression correlated with high-grade tumors and the presence of lymph node metastasis, as compared to patients' tumors with high nuclear pp32 expression. Although pp32 expression levels did not enhance the predictive power of cytoplasmic HuR status, nuclear pp32 levels and cytoplasmic HuR levels associated significantly in patient samples. Thus, we provide novel evidence that the tumor suppressor function of pp32 can be attributed to its ability to disrupt HuR binding to target mRNAs encoding key proteins for cancer cell survival and drug efficacy

Clinical use of alumina-toughened zirconia abutments for implant-supported restoration: prospective cohort study of survival analysis

Objectives The aim of this prospective cohort study was to compute the long-term clinical survival and complication rates of alumina-toughened zirconia abutments used for implant-supported restorations and to evaluate the effects of several clinical variables on these rates. Material and methods From May 1998 to September 2010, 213 patients aged 18years or older were recruited. The patients received 611 external hex implants and 328 implant-supported fixed restorations using alumina-toughened zirconia abutments. During the follow-up, each restoration was coded as a dental event, which included loosening or fracture of abutment screws, and abutment fracture. From the coded data, the effects of the investigated clinical variablesrestored area (anterior/posterior), number of prosthodontic units (one/two units or over), prosthesis type (single-unit/multiunit without pontic/multiunit with pontic), implant system, and patient genderon the survival of the abutments were evaluated. Survival analysis using KaplanMeier method and Cox proportional hazard model was applied. The 5-year survival and complication rates of the abutments were assessed. Results The number of prosthodontic units and the type of prosthesis had a significant association with complication rates (P<0.05). KaplanMeier survival analysis estimated that the cumulative 5-year complication rate of the abutments used in single restorations was 19.7%. Multiunit-fixed dental prostheses without and with pontics had complication rates of 3.9% and 3.8%, respectively. The 5-year survival rate of the abutments was more than 95%, regardless of the type of prosthesis. Conclusions Alumina-toughened zirconia abutments are likely to exhibit excellent long-term survival in clinical use for fixed restorations. Single tooth replacement with the abutment at the molar region may require special care and extra attention.OAIID:oai:osos.snu.ac.kr:snu2013-01/102/0000030821/3SEQ:3PERF_CD:SNU2013-01EVAL_ITEM_CD:102USER_ID:0000030821ADJUST_YN:YEMP_ID:A076080DEPT_CD:861CITE_RATE:2.514FILENAME:2013 05월 coir 24(5),2013,517-522.pdfDEPT_NM:치의학과EMAIL:[email protected]_YN:YCONFIRM:

Trends and predictions of metabolic risk factors for acute myocardial infarction: findings from a multiethnic nationwide cohort

BACKGROUND: Understanding the trajectories of metabolic risk factors for acute myocardial infarction (AMI) is necessary for healthcare policymaking. We estimated future projections of the incidence of metabolic diseases in a multi-ethnic population with AMI. METHODS: The incidence and mortality contributed by metabolic risk factors in the population with AMI (diabetes mellitus [T2DM], hypertension, hyperlipidemia, overweight/obesity, active/previous smokers) were projected up to year 2050, using linear and Poisson regression models based on the Singapore Myocardial Infarction Registry from 2007 to 2018. Forecast analysis was stratified based on age, sex and ethnicity. FINDINGS: From 2025 to 2050, the incidence of AMI is predicted to rise by 194.4% from 482 to 1418 per 100,000 population. The largest percentage increase in metabolic risk factors within the population with AMI is projected to be overweight/obesity (880.0% increase), followed by hypertension (248.7% increase), T2DM (215.7% increase), hyperlipidemia (205.0% increase), and active/previous smoking (164.8% increase). The number of AMI-related deaths is expected to increase by 294.7% in individuals with overweight/obesity, while mortality is predicted to decrease by 11.7% in hyperlipidemia, 29.9% in hypertension, 32.7% in T2DM and 49.6% in active/previous smokers, from 2025 to 2050. Compared with Chinese individuals, Indian and Malay individuals bear a disproportionate burden of overweight/obesity incidence and AMI-related mortality. INTERPRETATION: The incidence of AMI is projected to continue rising in the coming decades. Overweight/obesity will emerge as fastest-growing metabolic risk factor and the leading risk factor for AMI-related mortality. FUNDING: This research was supported by the NUHS Seed Fund (NUHSRO/2022/058/RO5+6/Seed-Mar/03) and National Medical Research Council Research Training Fellowship (MOH-001131). The SMIR is a national, ministry-funded registry run by the National Registry of Diseases Office and funded by the Ministry of Health, Singapore

Percutaneous endoscopic lumbar discectomy: clinical and quality of life outcomes with a minimum 2 year follow-up

<p>Abstract</p> <p>Background</p> <p>Percutaneous endoscopic lumbar discectomy is a relatively new technique. Very few studies have reported the clinical outcome of percutaneous endoscopic discectomy in terms of quality of life and return to work.</p> <p>Method</p> <p>55 patients with percutaneous endoscopic lumbar discectomy done from 2002 to 2006 had their clinical outcomes reviewed in terms of the North American Spine Score (NASS), Medical Outcomes Study Short Form-36 scores (SF-36) and Pain Visual Analogue Scale (VAS) and return to work.</p> <p>Results</p> <p>The mean age was 35.6 years, the mean operative time was 55.8 minutes and the mean length of follow-up was 3.4 years. The mean hospital stay for endoscopic discectomy was 17.3 hours. There was significant reduction in the severity of back pain and lower limb symptoms (NASS and VAS, p < 0.05) at 6 months and 2 years. There was significant improvement in all aspects of the Quality of Life (SF-36, p < 0.05) scores except for general health at 6 months and 2 years postoperation. The recurrence rate was 5% (3 patients). 5% (3 patients) subsequently underwent lumbar fusion for persistent back pain. All patients returned to their previous occupation after surgery at a mean time of 24.3 days.</p> <p>Conclusion</p> <p>Percutaneous endoscopic lumbar discectomy is associated with improvement in back pain and lower limb symptoms postoperation which translates to improvement in quality of life. It has the advantage that it can be performed on a day case basis with short length of hospitalization and early return to work thus improving quality of life earlier.</p

A shape tailored gold-conductive polymer nanocomposite as a transparent electrode with extraordinary insensitivity to volatile organic compounds (VOCs)

In this study, the transparent conducting polymer of poly (3,4-ethylenendioxythiophene): poly(styrene sulphonate) (PEDOT:PSS) was nanohybridized via inclusion of gold nanofillers including nanospheres (NSs) and nanorods (NRs). Such nanocomposite thin films offer not only more optimum conductivity than the pristine polymer but also excellent resistivity against volatile organic compounds (VOCs). Interestingly, such amazing properties are achieved in the diluted regimes of the nanofillers and depend on the characteristics of the interfacial region of the polymer and nanofillers, i.e. the aspect ratio of the latter component. Accordingly, a shape dependent response is made that is more desirable in case of using the Au nanorods with a much larger aspect ratio than their nanosphere counterparts. This transparent nanocomposite thin film with an optimized conductivity and very low sensitivity to organic gases is undoubtedly a promising candidate material for the touch screen panel production industry. Considering PEDOT as a known material for integrated electrodes in energy saving applications, we believe that our strategy might be an important progress in the field.Peer reviewe