59 research outputs found

    Finishing the euchromatic sequence of the human genome

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    The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

    Large expert-curated database for benchmarking document similarity detection in biomedical literature search

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    Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

    Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

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    Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

    Vertically-Aligned Single-Crystal Nanocone Arrays: Controlled Fabrication and Enhanced Field Emission

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    Metal nanostructures with conical shape, vertical alignment, large ratio of cone height and curvature radius at the apex, controlled cone angle, and single-crystal structure are ideal candidates for enhancing field electron-emission efficiency with additional merits, such as good mechanical and thermal stability. However, fabrication of such nanostructures possessing all these features is challenging. Here, we report on the controlled fabrication of large scale, vertically aligned, and mechanically self-supported single-crystal Cu nanocones with controlled cone angle and enhanced field emission. The Cu nanocones were fabricated by ion-track templates in combination with electrochemical deposition. Their cone angle is controlled in the range from 0.3° to 6.2° by asymmetrically selective etching of the ion tracks and the minimum tip curvature diameter reaches down to 6 nm. The field emission measurements show that the turn-on electric field of the Cu nanocone field emitters can be as low as 1.9 V/μm at current density of 10 μA/cm2 (a record low value for Cu nanostructures, to the best of our knowledge). The maximum field enhancement factor we measured was as large as 6068, indicating that the Cu nanocones are promising candidates for field emission applications.Department of Applied Physic

    Association of maximum weight with hyperuricemia risk: a retrospective study of 21,414 Chinese people.

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    BACKGROUND: Obesity has been demonstrated to be associated with increased serum uric acid (SUA); however, little is known regarding the relationship between maximum weight, or maximum weight fluctuation, and uric acid concentration. Through retrospective means, we determined the association of maximum weight with SUA risk. METHODS: Data of 21,414 participants (8,630 males and 12,784 females) from the 2007-8 China National Diabetes and Metabolic Disorders Study were analyzed for parameters including lifestyle habits, biochemical blood analysis and self-reported maximum weight. RESULTS: Elevated SUA subjects shared a cluster of demographic features. After adjustment for age, gender, education, smoking, drinking, physical activity, WHR, height, eGFR(evaluate glomerular filtration rate), and diuretic usage, multivariate logistic regression models demonstrated maximum weight was associated with increased risk of elevated SUA level (P<0.001). Duration of maximum weight was related with decreased risk of elevated SUA level (P<0.001). There was a significant correlation between time of weight loss and risk of increased SUA level reduction (P<0.001). Furthermore, our data indicated that the degree of weight loss from maximum weight was another important factor for the risk of increased SUA level reduction (P<0.001). Finally, ROC curve analysis revealed area under the curve was 0.661 (95% CI, 0.647-0.674), statistically significant for maximum weight association with hyperuricemia (P<0.001). CONCLUSIONS: Maximum weight is a strong risk factor for increased uric acid level in the Chinese population, which might serve as a novel clinical indicator suggesting hyperuricemia. Controlling maximum weight, keeping weight to the appropriate range, and maintaining the stable weight may be conducive for decreasing risk of hyperuricemia

    Table_4_Impact of type 2 diabetes mellitus on the prognosis of patients with hepatocellular carcinoma after laparoscopic liver resection: A multicenter retrospective study.docx

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    BackgroundThe effect of type 2 diabetes mellitus (T2DM) on survival of patients with hepatocellular carcinoma (HCC) after laparoscopic liver resection (LLR) has not been reported. This study aimed to explore the relationship between preoperative T2DM and long-term prognosis in HCC patients undergoing LLR.MethodsHCC patients receiving LLR as initial treatment at four cancer centers were retrospectively included in this study. Clinicopathological factors associated with the prognosis of HCC patients were identified using univariate and multivariate Cox regression analysis. Recurrence-free survival (RFS) and overall survival (OS) curves between different cohorts of patients were generated using the Kaplan-Meier method and compared using the log-rank test.ResultsOf 402 HCC patients included, 62 patients had T2DM and 340 patients did not have T2DM. The OS and RFS of patients with T2DM were significantly worse compared to those without T2DM (P = 0.001 and 0.032, respectively). In Cox multivariate analysis, T2DM was identified as an independent risk factors for OS (HR = 2.31, 95% CI = 1.38–3.85, P = 0.001) and RFS (HR = 1.66, 95% CI = 1.08–2.55, P = 0.020).ConclusionsFollowing laparoscopic surgical approach, HCC patients with T2DM had poorer prognoses than those without T2DM. Preoperative T2DM was an independent risk factor for HCC patients. Thus, patients with concurrent HCC and T2DM should be closely monitored after LLR.</p

    Table_2_Impact of type 2 diabetes mellitus on the prognosis of patients with hepatocellular carcinoma after laparoscopic liver resection: A multicenter retrospective study.docx

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    BackgroundThe effect of type 2 diabetes mellitus (T2DM) on survival of patients with hepatocellular carcinoma (HCC) after laparoscopic liver resection (LLR) has not been reported. This study aimed to explore the relationship between preoperative T2DM and long-term prognosis in HCC patients undergoing LLR.MethodsHCC patients receiving LLR as initial treatment at four cancer centers were retrospectively included in this study. Clinicopathological factors associated with the prognosis of HCC patients were identified using univariate and multivariate Cox regression analysis. Recurrence-free survival (RFS) and overall survival (OS) curves between different cohorts of patients were generated using the Kaplan-Meier method and compared using the log-rank test.ResultsOf 402 HCC patients included, 62 patients had T2DM and 340 patients did not have T2DM. The OS and RFS of patients with T2DM were significantly worse compared to those without T2DM (P = 0.001 and 0.032, respectively). In Cox multivariate analysis, T2DM was identified as an independent risk factors for OS (HR = 2.31, 95% CI = 1.38–3.85, P = 0.001) and RFS (HR = 1.66, 95% CI = 1.08–2.55, P = 0.020).ConclusionsFollowing laparoscopic surgical approach, HCC patients with T2DM had poorer prognoses than those without T2DM. Preoperative T2DM was an independent risk factor for HCC patients. Thus, patients with concurrent HCC and T2DM should be closely monitored after LLR.</p

    Table_3_Impact of type 2 diabetes mellitus on the prognosis of patients with hepatocellular carcinoma after laparoscopic liver resection: A multicenter retrospective study.docx

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    BackgroundThe effect of type 2 diabetes mellitus (T2DM) on survival of patients with hepatocellular carcinoma (HCC) after laparoscopic liver resection (LLR) has not been reported. This study aimed to explore the relationship between preoperative T2DM and long-term prognosis in HCC patients undergoing LLR.MethodsHCC patients receiving LLR as initial treatment at four cancer centers were retrospectively included in this study. Clinicopathological factors associated with the prognosis of HCC patients were identified using univariate and multivariate Cox regression analysis. Recurrence-free survival (RFS) and overall survival (OS) curves between different cohorts of patients were generated using the Kaplan-Meier method and compared using the log-rank test.ResultsOf 402 HCC patients included, 62 patients had T2DM and 340 patients did not have T2DM. The OS and RFS of patients with T2DM were significantly worse compared to those without T2DM (P = 0.001 and 0.032, respectively). In Cox multivariate analysis, T2DM was identified as an independent risk factors for OS (HR = 2.31, 95% CI = 1.38–3.85, P = 0.001) and RFS (HR = 1.66, 95% CI = 1.08–2.55, P = 0.020).ConclusionsFollowing laparoscopic surgical approach, HCC patients with T2DM had poorer prognoses than those without T2DM. Preoperative T2DM was an independent risk factor for HCC patients. Thus, patients with concurrent HCC and T2DM should be closely monitored after LLR.</p
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