29 results on '"Youna Hu"'
Search Results
2. Correction: Whole exome sequencing reveals HSPA1L as a genetic risk factor for spontaneous preterm birth.
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Johanna M Huusko, Minna K Karjalainen, Britney E Graham, Ge Zhang, Emily G Farrow, Neil A Miller, Bo Jacobsson, Haley R Eidem, Jeffrey C Murray, Bruce Bedell, Patrick Breheny, Noah W Brown, Frans L Bødker, Nadia K Litterman, Pan-Pan Jiang, Laura Russell, David A Hinds, Youna Hu, andMe Research Team, Antonis Rokas, Kari Teramo, Kaare Christensen, Scott M Williams, Mika Rämet, Stephen F Kingsmore, Kelli K Ryckman, Mikko Hallman, and Louis J Muglia
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Genetics ,QH426-470 - Abstract
[This corrects the article DOI: 10.1371/journal.pgen.1007394.].
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- 2018
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3. Whole exome sequencing reveals HSPA1L as a genetic risk factor for spontaneous preterm birth.
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Johanna M Huusko, Minna K Karjalainen, Britney E Graham, Ge Zhang, Emily G Farrow, Neil A Miller, Bo Jacobsson, Haley R Eidem, Jeffrey C Murray, Bruce Bedell, Patrick Breheny, Noah W Brown, Frans L Bødker, Nadia K Litterman, Pan-Pan Jiang, Laura Russell, David A Hinds, Youna Hu, andMe Research Team, Antonis Rokas, Kari Teramo, Kaare Christensen, Scott M Williams, Mika Rämet, Stephen F Kingsmore, Kelli K Ryckman, Mikko Hallman, and Louis J Muglia
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Genetics ,QH426-470 - Abstract
Preterm birth is a leading cause of morbidity and mortality in infants. Genetic and environmental factors play a role in the susceptibility to preterm birth, but despite many investigations, the genetic basis for preterm birth remain largely unknown. Our objective was to identify rare, possibly damaging, nucleotide variants in mothers from families with recurrent spontaneous preterm births (SPTB). DNA samples from 17 Finnish mothers who delivered at least one infant preterm were subjected to whole exome sequencing. All mothers were of northern Finnish origin and were from seven multiplex families. Additional replication samples of European origin consisted of 93 Danish sister pairs (and two sister triads), all with a history of a preterm delivery. Rare exonic variants (frequency
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- 2018
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4. Genome-Wide Association Analyses in 128,266 Individuals Identifies New Morningness and Sleep Duration Loci.
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Samuel E Jones, Jessica Tyrrell, Andrew R Wood, Robin N Beaumont, Katherine S Ruth, Marcus A Tuke, Hanieh Yaghootkar, Youna Hu, Maris Teder-Laving, Caroline Hayward, Till Roenneberg, James F Wilson, Fabiola Del Greco, Andrew A Hicks, Chol Shin, Chang-Ho Yun, Seung Ku Lee, Andres Metspalu, Enda M Byrne, Philip R Gehrman, Henning Tiemeier, Karla V Allebrandt, Rachel M Freathy, Anna Murray, David A Hinds, Timothy M Frayling, and Michael N Weedon
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Genetics ,QH426-470 - Abstract
Disrupted circadian rhythms and reduced sleep duration are associated with several human diseases, particularly obesity and type 2 diabetes, but until recently, little was known about the genetic factors influencing these heritable traits. We performed genome-wide association studies of self-reported chronotype (morning/evening person) and self-reported sleep duration in 128,266 white British individuals from the UK Biobank study. Sixteen variants were associated with chronotype (P
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- 2016
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5. Graph-based Multilingual Product Retrieval in E-Commerce Search.
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Hanqing Lu, Youna Hu, Tong Zhao 0002, Tony Wu, Yiwei Song, and Bing Yin
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- 2021
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6. Shareable Representations for Search Query Understanding.
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Mukul Kumar, Youna Hu, Will Headden, Rahul Goutam, Heran Lin, and Bing Yin
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- 2020
7. RVTESTS: an efficient and comprehensive tool for rare variant association analysis using sequence data.
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Xiaowei Zhan, Youna Hu, Bingshan Li, Gonçalo R. Abecasis, and Dajiang J. Liu
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- 2016
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8. Graph-based Multilingual Product Retrieval in E-commerce Search
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Tony Wu, Yiwei Song, Tong Zhao, Hanqing Lu, Bing Yin, and Youna Hu
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FOS: Computer and information sciences ,Computer Science - Computation and Language ,Information retrieval ,Computer science ,business.industry ,Graph based ,02 engineering and technology ,E-commerce ,020204 information systems ,0202 electrical engineering, electronic engineering, information engineering ,Production (economics) ,Graph (abstract data type) ,Revenue ,020201 artificial intelligence & image processing ,Language model ,Product (category theory) ,business ,Computation and Language (cs.CL) ,Transformer (machine learning model) - Abstract
Nowadays, with many e-commerce platforms conducting global business, e-commerce search systems are required to handle product retrieval under multilingual scenarios. Moreover, comparing with maintaining per-country specific e-commerce search systems, having a universal system across countries can further reduce the operational and computational costs, and facilitate business expansion to new countries. In this paper, we introduce a universal end-to-end multilingual retrieval system, and discuss our learnings and technical details when training and deploying the system to serve billion-scale product retrieval for e-commerce search. In particular, we propose a multilingual graph attention based retrieval network by leveraging recent advances in transformer-based multilingual language models and graph neural network architectures to capture the interactions between search queries and items in e-commerce search. Offline experiments on five countries data show that our algorithm outperforms the state-of-the-art baselines by 35% recall and 25% mAP on average. Moreover, the proposed model shows significant increase of conversion/revenue in online A/B experiments and has been deployed in production for multiple countries., Comment: Accepted by 2021 Annual Conference of the North American Chapter of the Association for Computational Linguistics (NAACL 2021)
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- 2021
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9. A Study on the Effects of Vacuum, Nitrogen, and Air Heat Treatments on Single-Chain Cellulose Based on a Molecular Dynamics Simulation
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Youna Hua, Wei Wang, Jingying Gao, Ning Li, and Zening Qu
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heat treatment ,cellulose ,molecular dynamics ,mechanical properties ,Plant ecology ,QK900-989 - Abstract
Employing molecular dynamics software, three models—vacuum–cellulose, nitrogen–cellulose, and air–cellulose—were built to clarify, via a microscopic perspective, the macroscopic changes in single-chain cellulose undergoing vacuum, nitrogen, and air heat treatments. Kinetic simulations were run following model equilibrium within the NPT system of 423, 443, 463, 483, and 503 K. The energy variations, cell parameters, densities, mean square displacements, hydrogen bonding numbers, and mechanical parameters were analyzed for the three models. The findings demonstrate that as the temperature climbed, the cellular characteristics among two models—the nitrogen and vacuum models—decreased and subsequently increased. The nitrogen model reached its lowest value at 443 K. In contrast, the vacuum model reached its minimum value at 463 K. The vacuum heat treatment may enhance the structural stability of the single-chain cellulose more effectively than the nitrogen and air treatments because it increases the number of hydrogen bonds within the cellulose chain and stabilizes the mean square displacement. Furthermore, the temperature has an impact on the mechanical characteristics of the cellulose amorphous zone; the maximum values of E and G for the vacuum and nitrogen models are found at 463 and 443 K, respectively. The Young’s modulus and shear modulus were consistently more significant for the vacuum model at either temperature, and the Poisson’s ratio was the opposite. Therefore, the vacuum heat treatment can better maintain wood stiffness and deformation resistance, thus improving wood utilization. These findings provide an essential theoretical basis for wood processing and modification, which can help optimize the heat treatment and enhance wood’s utilization and added value.
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- 2024
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10. GWAS of self-reported mosquito bite size, itch intensity and attractiveness to mosquitoes implicates immune-related predisposition loci
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Alex Gutteridge, Xing Chen, Eric B. Fauman, Serena Scollen, Melissa R. Miller, Mera Tilley, David A. Hinds, Craig L. Hyde, Youna Hu, Amy V. Jones, Donal Gorman, Daniel Ziemek, Chao Tian, Peter J. Cox, and Michael W. Nagle
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0301 basic medicine ,Attractiveness ,Genotype ,T-Lymphocytes ,Genome-wide association study ,Biology ,Polymorphism, Single Nucleotide ,Insect bites and stings ,03 medical and health sciences ,0302 clinical medicine ,Polymorphism (computer science) ,parasitic diseases ,Genetics ,medicine ,Animals ,Humans ,Genetic Predisposition to Disease ,Association Studies Article ,Molecular Biology ,Gene ,Genetics (clinical) ,Genetic association ,Pruritus ,Insect Bites and Stings ,General Medicine ,medicine.disease ,Phenotype ,Culicidae ,030104 developmental biology ,Self Report ,030217 neurology & neurosurgery ,Genome-Wide Association Study - Abstract
Understanding the interaction between humans and mosquitoes is a critical area of study due to the phenomenal burdens on public health from mosquito-transmitted diseases. In this study, we conducted the first genome-wide association studies (GWAS) of self-reported mosquito bite reaction size (n = 84,724), itchiness caused by bites (n = 69,057), and perceived attractiveness to mosquitoes (n = 16,576). In total, 15 independent significant (P
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- 2017
11. Genetic Associations With Gestational Duration and Spontaneous Preterm Birth
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David A. Hinds, Bjarke Feenstra, Bo Jacobsson, Nadia K. Litterman, Mika Rämet, Kelli K Ryckman, Lisa M. Muglia, Youna Hu, Jamie Maziarz, Minna K. Karjalainen, Leah C. Kottyan, Carmy Forney, Mauris C. Nnamani, Daniel Miller, Johanna M. Huusko, Matthew T. Weirauch, Ellen A. Nohr, Allison Momany, George Davey Smith, Frank Geller, Xueping Liu, Bruce Bedell, Aarno Palotie, Mihaela Pavlicev, Arun R. Chavan, Louis J. Muglia, Pan Pan Jiang, Kari Teramo, Heather A. Boyd, Mads Melbye, Mikko Hallman, Verena Sengpiel, Günter P. Wagner, Julius Juodakis, Xiaoting Chen, Jonas Bacelis, Ge Zhang, Laura Russell, Institute for Molecular Medicine Finland, Aarno Palotie / Principal Investigator, University of Helsinki, HUS Gynecology and Obstetrics, Department of Obstetrics and Gynecology, Genomics of Neurological and Neuropsychiatric Disorders, Lääketieteen ja biotieteiden tiedekunta - Faculty of Medicine and Life Sciences, and Tampere University
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0301 basic medicine ,ras Proteins/genetics ,LOCI ,Datasets as Topic ,Physiology ,Genome-wide association study ,VARIANTS ,SUSCEPTIBILITY ,Bioinformatics ,0302 clinical medicine ,Polymorphism (computer science) ,single nucleotide polymorphism ,3123 Gynaecology and paediatrics ,Wnt4 Protein ,Pregnancy ,030202 anesthesiology ,Medicine ,RISK ,030219 obstetrics & reproductive medicine ,Obstetrics ,Receptor, Angiotensin, Type 2/genetics ,Gestational age ,Obstetrics and Gynecology ,Naisten- ja lastentaudit - Gynaecology and paediatrics ,General Medicine ,Adenylyl Cyclases/genetics ,DIFFERENTIATION ,Phenotype ,Duration (music) ,Premature Birth ,Regression Analysis ,Gestation ,Female ,Research Article ,Adenylyl Cyclases ,medicine.medical_specialty ,Biolääketieteet - Biomedicine ,Gestational Age ,Receptor, Angiotensin, Type 2 ,Polymorphism, Single Nucleotide ,Trans-Activators/genetics ,03 medical and health sciences ,AGE ,genomewide association ,Genetiikka, kehitysbiologia, fysiologia - Genetics, developmental biology, physiology ,Genetic variation ,Humans ,Genetic Predisposition to Disease ,Continuous trait ,GENOME-WIDE ASSOCIATION ,POLYMORPHISMS ,business.industry ,ENDOMETRIOSIS ,Genetic variants ,preterm birth ,Genetic Variation ,Gestational length ,Premature Birth/genetics ,medicine.disease ,Peptide Elongation Factors ,030104 developmental biology ,3121 General medicine, internal medicine and other clinical medicine ,Peptide Elongation Factors/genetics ,Genomewide association ,Trans-Activators ,ras Proteins ,WEIGHT ,3111 Biomedicine ,Wnt4 Protein/genetics ,business ,030217 neurology & neurosurgery ,Genome-Wide Association Study - Abstract
Background: Despite evidence that genetic factors contribute to the duration of gestation and the risk of preterm birth, robust associations with genetic variants have not been identified. We used large data sets that included the gestational duration to determine possible genetic associations. Methods: We performed a genomewide association study in a discovery set of samples obtained from 43,568 women of European ancestry using gestational duration as a continuous trait and term or preterm (
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- 2018
12. Genome-wide association analysis of pain severity in dysmenorrhea identifies association at chromosome 1p13.2, near the nerve growth factor locus
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Craig L. Hyde, Gordon McMurray, Ana Sredic-Rhodes, David A. Hinds, Youna Hu, Donal Gorman, Amy V. Jones, James Bilsland, Nicholas A. Furlotte, Serena Scollen, James R.F. Hockley, and Peter J. Cox
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0301 basic medicine ,Pelvic pain syndrome ,Adult ,Genome-wide association study ,Adolescent ,Childbearing Potential ,Locus (genetics) ,Bioinformatics ,Polymorphism, Single Nucleotide ,Cohort Studies ,03 medical and health sciences ,Family studies ,Young Adult ,Dysmenorrhea ,Nerve Growth Factor ,Genome-Wide Association Analysis ,Genetic predisposition ,Medicine ,Humans ,Pain Measurement ,Genetics ,business.industry ,Age Factors ,Dysmenorrhea pain severity ,Middle Aged ,030104 developmental biology ,Anesthesiology and Pain Medicine ,Nerve growth factor ,Neurology ,nervous system ,Chromosomes, Human, Pair 1 ,Pain severity ,NGF locus ,Female ,Neurology (clinical) ,business ,Research Paper - Abstract
Supplemental Digital Content is Available in the Text. Genome-wide association study on 11,891 females of European descent for self-reported dysmenorrhea pain severity identified a significant association that colocalises with the NGF locus., Dysmenorrhea is a common chronic pelvic pain syndrome affecting women of childbearing potential. Family studies suggest that genetic background influences the severity of dysmenorrhea, but genetic predisposition and molecular mechanisms underlying dysmenorrhea are not understood. In this study, we conduct the first genome-wide association study to identify genetic factors associated with dysmenorrhea pain severity. A cohort of females of European descent (n = 11,891) aged 18 to 45 years rated their average dysmenorrhea pain severity. We used a linear regression model adjusting for age and body mass index, identifying one genome-wide significant (P < 5 × 10−8) association (rs7523086, P = 4.1 × 10−14, effect size 0.1 [95% confidence interval, 0.074–0.126]). This single nucleotide polymorphism is colocalising with NGF, encoding nerve growth factor. The presence of one risk allele corresponds to a predicted 0.1-point increase in pain intensity on a 4-point ordinal pain scale. The putative effects on NGF function and/or expression remain unknown. However, genetic variation colocalises with active epigenetic marks in fat and ovary tissues, and expression levels in aorta tissue of a noncoding RNA flanking NGF correlate. Participants reporting extreme dysmenorrhea pain were more likely to report being positive for endometriosis, polycystic ovarian syndrome, depression, and other psychiatric disorders. Our results indicate that dysmenorrhea pain severity is partly genetically determined. NGF already has an established role in chronic pain disorders, and our findings suggest that NGF may be an important mediator for gynaecological/pelvic pain in the viscera.
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- 2016
13. Genome-wide association analyses in >119,000 individuals identifies thirteen morningness and two sleep duration loci
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James F. Wilson, Seung Ku Lee, Samuel E. Jones, Rachel M. Freathy, Enda M. Byrne, Jessica Tyrrell, Hanieh Yaghootkar, Maris Teder-Laving, Caroline Hayward, Karla V. Allebrandt, Timothy M. Frayling, Fabiola M. Del Greco, Till Roenneberg, David A. Hinds, Marcus A. Tuke, Chang-Ho Yun, Philip R. Gehrman, Anna Murray, Katherine S. Ruth, Robin N Beaumont, Andrew A. Hicks, Youna Hu, Chol Shin, Andres Metspalu, Andrew R. Wood, Henning Tiemeier, and Michael N. Weedon
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0303 health sciences ,medicine.medical_specialty ,Evening ,business.industry ,Chronotype ,Physiology ,Genome-wide association study ,medicine.disease ,Obesity ,3. Good health ,PER2 ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Internal medicine ,Medicine ,Circadian rhythm ,Allele ,business ,030217 neurology & neurosurgery ,030304 developmental biology ,Morning - Abstract
Disrupted circadian rhythms and reduced sleep duration are associated with several human diseases, particularly obesity and type 2 diabetes, but little is known about the genetic factors influencing these heritable traits. We performed genome-wide association studies of self-reported chronotype (morning/evening person) and self-reported sleep duration in 128,266 White British individuals from the UK Biobank study. Sixteen variants were associated with chronotype (P
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- 2016
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14. Sample size determination for quadratic inference functions in longitudinal design with dichotomous outcomes
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Peter X.-K. Song and Youna Hu
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Statistics and Probability ,Clinical Trials as Topic ,Models, Statistical ,Epidemiology ,Covariance matrix ,Inference ,Numerical Analysis, Computer-Assisted ,Marginal model ,Wald test ,Statistical power ,Sample size determination ,Sample Size ,Statistics ,Covariate ,Humans ,Longitudinal Studies ,Generalized estimating equation ,Mathematics - Abstract
Quadratic inference functions (QIF) methodology is an important alternative to the generalized estimating equations (GEE) method in the longitudinal marginal model, as it offers higher estimation efficiency than the GEE when correlation structure is misspecified. The focus of this paper is on sample size determination and power calculation for QIF based on the Wald test in a marginal logistic model with covariates of treatment, time, and treatment-time interaction. We have made three contributions in this paper: (i) we derived formulas of sample size and power for QIF and compared their performance with those given by the GEE; (ii) we proposed an optimal scheme of sample size determination to overcome the difficulty of unknown true correlation matrix in the sense of minimal average risk; and (iii) we studied properties of both QIF and GEE sample size formulas in relation to the number of follow-up visits and found that the QIF gave more robust sample sizes than the GEE. Using numerical examples, we illustrated that without sacrificing statistical power, the QIF design leads to sample size saving and hence lower study cost in comparison with the GEE analysis. We conclude that the QIF analysis is appealing for longitudinal studies.
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- 2012
15. Transition from donor candidates to live kidney donors: the impact of race and undiagnosed medical disease states
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Youna Hu, Peter X.-K. Song, Akinlolu O. Ojo, and Silas P. Norman
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Transplantation ,medicine.medical_specialty ,business.industry ,Renal function ,Ethnic origin ,medicine.disease ,Surgery ,Donation ,Internal medicine ,medicine ,Young adult ,Prospective cohort study ,business ,Contraindication ,Kidney transplantation - Abstract
Background: Living kidney donors (LKD) allow for increased access to lifesaving organs for transplantation. There is a relative paucity of African American (AA) live kidney donors. The prevalence of medical disease in LKD candidates has not been well studied. We examined the medical limitations to living kidney donation in a large Midwestern transplant center. Methods: A total of 2519 adults (age ‡ 18 ) evaluated as potential LKD (PD) between January 1, 1996 and June 30, 2006 were prospectively followed until evaluation outcome (completed live donation, medical exclusion from live donation, non-medical exclusion from live donation). Logistic regression was used to examine the effect of age on donor exclusion, and chi-square tests were used to compare the likelihood of donor exclusions between racial and gender groups. Results: Sixty percent of PD were female (n = 1300), and 86% were Caucasian (CA) (n = 1862). Overall, 48.7% of PD who underwent evaluation became LKD. The odds of donation were 52% lower in AA compared to CA (OR 0.48 p < 0.001). Among PD excluded from dona- tion, the most common medical diagnoses were hypertension (HTN) (24.7%), inadequate creatinine clearance (10.6%) and a positive final crossmatch (10.5%). The rate of PD exclusion for obesity was twofold higher in AA compared to CA (12.8% vs. 5.8%, p < 0.001). Conclusions: Hypertension in PD is equally significant barrier to living kidney donation in AA and CA whereas obesity is a greater barrier in AA.
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- 2011
16. RVTESTS: an efficient and comprehensive tool for rare variant association analysis using sequence data
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Youna Hu, Dajiang J. Liu, Gonçalo R. Abecasis, Xiaowei Zhan, and Bingshan Li
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0301 basic medicine ,Statistics and Probability ,Source code ,Genotype ,Computer science ,media_common.quotation_subject ,computer.software_genre ,Biochemistry ,Set (abstract data type) ,03 medical and health sciences ,0302 clinical medicine ,Bioinformatics databases ,Genetic variation ,Animals ,Humans ,1000 Genomes Project ,Molecular Biology ,Allele frequency ,Gene ,Sequence (medicine) ,media_common ,Genetics and Population Analysis ,Genetic Variation ,High-Throughput Nucleotide Sequencing ,Applications Notes ,Computer Science Applications ,Computational Mathematics ,030104 developmental biology ,Computational Theory and Mathematics ,Programming Languages ,Data mining ,computer ,030217 neurology & neurosurgery ,Software - Abstract
Motivation: Next-generation sequencing technologies have enabled the large-scale assessment of the impact of rare and low-frequency genetic variants for complex human diseases. Gene-level association tests are often performed to analyze rare variants, where multiple rare variants in a gene region are analyzed jointly. Applying gene-level association tests to analyze sequence data often requires integrating multiple heterogeneous sources of information (e.g. annotations, functional prediction scores, allele frequencies, genotypes and phenotypes) to determine the optimal analysis unit and prioritize causal variants. Given the complexity and scale of current sequence datasets and bioinformatics databases, there is a compelling need for more efficient software tools to facilitate these analyses. To answer this challenge, we developed RVTESTS, which implements a broad set of rare variant association statistics and supports the analysis of autosomal and X-linked variants for both unrelated and related individuals. RVTESTS also provides useful companion features for annotating sequence variants, integrating bioinformatics databases, performing data quality control and sample selection. We illustrate the advantages of RVTESTS in functionality and efficiency using the 1000 Genomes Project data. Availability and implementation: RVTESTS is available on Linux, MacOS and Windows. Source code and executable files can be obtained at https://github.com/zhanxw/rvtests Contact: zhanxw@gmail.com; goncalo@umich.edu; dajiang.liu@outlook.com Supplementary information: Supplementary data are available at Bioinformatics online.
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- 2015
17. GWAS of 89,283 individuals identifies genetic variants associated with self-reporting of being a morning person
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Youna Hu, Nicholas Eriksson, Joyce Y. Tung, Alena Shmygelska, David A. Hinds, and David H. Tran
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0301 basic medicine ,Adult ,Male ,Science ,General Physics and Astronomy ,Genome-wide association study ,Biology ,Polymorphism, Single Nucleotide ,General Biochemistry, Genetics and Molecular Biology ,Article ,Body Mass Index ,03 medical and health sciences ,Sleep Apnea Syndromes ,Orexin Receptors ,Sleep Initiation and Maintenance Disorders ,Genetic variation ,Humans ,Circadian rhythm ,Genetic association ,Genetics ,Multidisciplinary ,Depression ,F-Box Proteins ,Genetic Variation ,Mendelian Randomization Analysis ,General Chemistry ,Period Circadian Proteins ,Middle Aged ,Circadian Rhythm ,PER2 ,PER3 ,030104 developmental biology ,ras Proteins ,Commentary ,Female ,RGS Proteins ,Genome-Wide Association Study ,Vasoactive Intestinal Peptide - Abstract
Circadian rhythms are a nearly universal feature of living organisms and affect almost every biological process. Our innate preference for mornings or evenings is determined by the phase of our circadian rhythms. We conduct a genome-wide association analysis of self-reported morningness, followed by analyses of biological pathways and related phenotypes. We identify 15 significantly associated loci, including seven near established circadian genes (rs12736689 near RGS16, P=7.0 × 10−18; rs9479402 near VIP, P=3.9 × 10−11; rs55694368 near PER2, P=2.6 × 10−9; rs35833281 near HCRTR2, P=3.7 × 10−9; rs11545787 near RASD1, P=1.4 × 10−8; rs11121022 near PER3, P=2.0 × 10−8; rs9565309 near FBXL3, P=3.5 × 10−8. Circadian and phototransduction pathways are enriched in our results. Morningness is associated with insomnia and other sleep phenotypes; and is associated with body mass index and depression but we did not find evidence for a causal relationship in our Mendelian randomization analysis. Our findings reinforce current understanding of circadian biology and will guide future studies., Circadian rhythms and related behaviours vary across individuals. Here, a large genome-wide association study reveals common single nucleotide variants influencing whether an individual reports as being a ‘morning person' by identifying 15 significant loci, including 7 near known circadian genes.
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- 2014
18. Whole-exome sequencing identifies rare and low-frequency coding variants associated with LDL cholesterol
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Leslie A. Lange, Youna Hu, He Zhang, Chenyi Xue, Ellen M. Schmidt, Zheng-Zheng Tang, Chris Bizon, Ethan M. Lange, Joshua D. Smith, Emily H. Turner, Goo Jun, Hyun Min Kang, Gina Peloso, Paul Auer, Kuo-ping Li, Jason Flannick, Ji Zhang, Christian Fuchsberger, Kyle Gaulton, Cecilia Lindgren, Adam Locke, Alisa Manning, Xueling Sim, Manuel A. Rivas, Oddgeir L. Holmen, Omri Gottesman, Yingchang Lu, Douglas Ruderfer, Eli A. Stahl, Qing Duan, Yun Li, Peter Durda, Shuo Jiao, Aaron Isaacs, Albert Hofman, Joshua C. Bis, Adolfo Correa, Michael E. Griswold, Johanna Jakobsdottir, Albert V. Smith, Pamela J. Schreiner, Mary F. Feitosa, Qunyuan Zhang, Jennifer E. Huffman, Jacy Crosby, Christina L. Wassel, Ron Do, Nora Franceschini, Lisa W. Martin, Jennifer G. Robinson, Themistocles L. Assimes, David R. Crosslin, Elisabeth A. Rosenthal, Michael Tsai, Mark J. Rieder, Deborah N. Farlow, Aaron R. Folsom, Thomas Lumley, Ervin R. Fox, Christopher S. Carlson, Ulrike Peters, Rebecca D. Jackson, Cornelia M. van Duijn, André G. Uitterlinden, Daniel Levy, Jerome I. Rotter, Herman A. Taylor, Vilmundur Gudnason, David S. Siscovick, Myriam Fornage, Ingrid B. Borecki, Caroline Hayward, Igor Rudan, Y. Eugene Chen, Erwin P. Bottinger, Ruth J.F. Loos, Pål Sætrom, Kristian Hveem, Michael Boehnke, Leif Groop, Mark McCarthy, Thomas Meitinger, Christie M. Ballantyne, Stacey B. Gabriel, Christopher J. O’Donnell, Wendy S. Post, Kari E. North, Alexander P. Reiner, Eric Boerwinkle, Bruce M. Psaty, David Altshuler, Sekar Kathiresan, Dan-Yu Lin, Gail P. Jarvik, L. Adrienne Cupples, Charles Kooperberg, James G. Wilson, Deborah A. Nickerson, Goncalo R. Abecasis, Stephen S. Rich, Russell P. Tracy, Cristen J. Willer, David M. Altshuler, Gonçalo R. Abecasis, Hooman Allayee, Sharon Cresci, Mark J. Daly, Paul I.W. de Bakker, Mark A. DePristo, Peter Donnelly, Tim Fennell, Kiran Garimella, Stanley L. Hazen, Daniel M. Jordan, Adam Kiezun, Guillaume Lettre, Bingshan Li, Mingyao Li, Christopher H. Newton-Cheh, Sandosh Padmanabhan, Sara Pulit, Daniel J. Rader, David Reich, Muredach P. Reilly, Steve Schwartz, Laura Scott, John A. Spertus, Nathaniel O. Stitziel, Nina Stoletzki, Shamil R. Sunyaev, Benjamin F. Voight, Ermeg Akylbekova, Larry D. Atwood, Maja Barbalic, R. Graham Barr, Emelia J. Benjamin, Joshua Bis, Donald W. Bowden, Jennifer Brody, Matthew Budoff, Greg Burke, Sarah Buxbaum, Jeff Carr, Donna T. Chen, Ida Y. Chen, Wei-Min Chen, Pat Concannon, Ralph D’Agostino, Anita L. DeStefano, Albert Dreisbach, Josée Dupuis, J. Peter Durda, Jaclyn Ellis, Caroline S. Fox, Ervin Fox, Vincent Funari, Santhi K. Ganesh, Julius Gardin, David Goff, Ora Gordon, Wayne Grody, Myron Gross, Xiuqing Guo, Ira M. Hall, Nancy L. Heard-Costa, Susan R. Heckbert, Nicholas Heintz, David M. Herrington, DeMarc Hickson, Jie Huang, Shih-Jen Hwang, David R. Jacobs, Nancy S. Jenny, Andrew D. Johnson, Craig W. Johnson, Steven Kawut, Richard Kronmal, Raluca Kurz, Martin G. Larson, Mark Lawson, Cora E. Lewis, Dalin Li, Honghuang Lin, Chunyu Liu, Jiankang Liu, Kiang Liu, Xiaoming Liu, Yongmei Liu, William T. Longstreth, Cay Loria, Kathryn Lunetta, Aaron J. Mackey, Rachel Mackey, Ani Manichaikul, Taylor Maxwell, Barbara McKnight, James B. Meigs, Alanna C. Morrison, Solomon K. Musani, Josyf C. Mychaleckyj, Jennifer A. Nettleton, Kari North, Daniel O’Leary, Frank Ong, Walter Palmas, James S. Pankow, Nathan D. Pankratz, Shom Paul, Marco Perez, Sharina D. Person, Joseph Polak, Aaron R. Quinlan, Leslie J. Raffel, Vasan S. Ramachandran, Kenneth Rice, Jill P. Sanders, Pamela Schreiner, Sudha Seshadri, Steve Shea, Stephen Sidney, Kevin Silverstein, Nicholas L. Smith, Nona Sotoodehnia, Asoke Srinivasan, Kent Taylor, Fridtjof Thomas, Michael Y. Tsai, Kelly A. Volcik, Chrstina L. Wassel, Karol Watson, Gina Wei, Wendy White, Kerri L. Wiggins, Jemma B. Wilk, O. Dale Williams, Gregory Wilson, Phillip Wolf, Neil A. Zakai, John Hardy, James F. Meschia, Michael Nalls, Andrew Singleton, Brad Worrall, Michael J. Bamshad, Kathleen C. Barnes, Ibrahim Abdulhamid, Frank Accurso, Ran Anbar, Terri Beaty, Abigail Bigham, Phillip Black, Eugene Bleecker, Kati Buckingham, Anne Marie Cairns, Daniel Caplan, Barbara Chatfield, Aaron Chidekel, Michael Cho, David C. Christiani, James D. Crapo, Julia Crouch, Denise Daley, Anthony Dang, Hong Dang, Alicia De Paula, Joan DeCelie-Germana, Allen DozorMitch Drumm, Maynard Dyson, Julia Emerson, Mary J. Emond, Thomas Ferkol, Robert Fink, Cassandra Foster, Deborah Froh, Li Gao, William Gershan, Ronald L. Gibson, Elizabeth Godwin, Magdalen Gondor, Hector Gutierrez, Nadia N. Hansel, Paul M. Hassoun, Peter Hiatt, John E. Hokanson, Michelle Howenstine, Laura K. Hummer, Jamshed Kanga, Yoonhee Kim, Michael R. Knowles, Michael Konstan, Thomas Lahiri, Nan Laird, Christoph Lange, Lin Lin, Xihong Lin, Tin L. Louie, David Lynch, Barry Make, Thomas R. Martin, Steve C. Mathai, Rasika A. Mathias, John McNamara, Sharon McNamara, Deborah Meyers, Susan Millard, Peter Mogayzel, Richard Moss, Tanda Murray, Dennis Nielson, Blakeslee Noyes, Wanda O’Neal, David Orenstein, Brian O’Sullivan, Rhonda Pace, Peter Pare, H. Worth Parker, Mary Ann Passero, Elizabeth Perkett, Adrienne Prestridge, Nicholas M. Rafaels, Bonnie Ramsey, Elizabeth Regan, Clement Ren, George Retsch-Bogart, Michael Rock, Antony Rosen, Margaret Rosenfeld, Ingo Ruczinski, Andrew Sanford, David Schaeffer, Cindy Sell, Daniel Sheehan, Edwin K. Silverman, Don Sin, Terry Spencer, Jackie Stonebraker, Holly K. Tabor, Laurie Varlotta, Candelaria I. Vergara, Robert Weiss, Fred Wigley, Robert A. Wise, Fred A. Wright, Mark M. Wurfel, Robert Zanni, Fei Zou, Phil Green, Jay Shendure, Joshua M. Akey, Carlos D. Bustamante, Evan E. Eichler, P. Keolu Fox, Wenqing Fu, Adam Gordon, Simon Gravel, Jill M. Johnsen, Mengyuan Kan, Eimear E. Kenny, Jeffrey M. Kidd, Fremiet Lara-Garduno, Suzanne M. Leal, Dajiang J. Liu, Sean McGee, Timothy D. O’Connor, Bryan Paeper, Peggy D. Robertson, Jeffrey C. Staples, Jacob A. Tennessen, Gao Wang, Qian Yi, Rebecca Jackson, Garnet Anderson, Hoda Anton-Culver, Paul L. Auer, Shirley Beresford, Henry Black, Robert Brunner, Robert Brzyski, Dale Burwen, Bette Caan, Cara L. Carty, Rowan Chlebowski, Steven Cummings, J. David Curb, Charles B. Eaton, Leslie Ford, Stephanie M. Fullerton, Margery Gass, Nancy Geller, Gerardo Heiss, Barbara V. Howard, Li Hsu, Carolyn M. Hutter, John Ioannidis, Karen C. Johnson, Lewis Kuller, Andrea LaCroix, Kamakshi Lakshminarayan, Dorothy Lane, Norman Lasser, Erin LeBlanc, Kuo-Ping Li, Marian Limacher, Benjamin A. Logsdon, Shari Ludlam, JoAnn E. Manson, Karen Margolis, Lisa Martin, Joan McGowan, Keri L. Monda, Jane Morley Kotchen, Lauren Nathan, Judith Ockene, Mary Jo O’Sullivan, Lawrence S. Phillips, Ross L. Prentice, John Robbins, Jacques E. Rossouw, Haleh Sangi-Haghpeykar, Gloria E. Sarto, Sally Shumaker, Michael S. Simon, Marcia L. Stefanick, Evan Stein, Hua Tang, Kira C. Taylor, Cynthia A. Thomson, Timothy A. Thornton, Linda Van Horn, Mara Vitolins, Jean Wactawski-Wende, Robert Wallace, Sylvia Wassertheil-Smoller, Donglin Zeng, Deborah Applebaum-Bowden, Michael Feolo, Weiniu Gan, Dina N. Paltoo, Phyliss Sholinsky, Anne Sturcke, Epidemiology, and Internal Medicine
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Male ,Genome-wide association study ,030204 cardiovascular system & hematology ,Cohort Studies ,0302 clinical medicine ,Gene Frequency ,Receptors ,Genotype ,Dyslipidemias/blood ,Receptors, LDL/genetics ,Genetics(clinical) ,Exome ,Genetics (clinical) ,Exome sequencing ,Genetics ,0303 health sciences ,Serine Endopeptidases ,Single Nucleotide ,Middle Aged ,3. Good health ,Cholesterol ,Phenotype ,Genetic Code ,Cholesterol, LDL/genetics ,Female ,lipids (amino acids, peptides, and proteins) ,Proprotein Convertases ,Proprotein Convertase 9 ,Sequence Analysis ,Adult ,Apolipoproteins E/blood ,LDL/genetics ,Serine Endopeptidases/genetics ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,Article ,03 medical and health sciences ,Apolipoproteins E ,SDG 3 - Good Health and Well-being ,Humans ,Polymorphism ,Allele frequency ,030304 developmental biology ,Genetic association ,Aged ,Dyslipidemias ,PCSK9 ,DNA ,Cholesterol, LDL ,Lipase ,Sequence Analysis, DNA ,Receptors, LDL ,Lipase/genetics ,Proprotein Convertases/genetics ,Follow-Up Studies ,Genome-Wide Association Study - Abstract
Elevated low-density lipoprotein cholesterol (LDL-C) is a treatable, heritable risk factor for cardiovascular disease. Genome-wide association studies (GWASs) have identified 157 variants associated with lipid levels but are not well suited to assess the impact of rare and low-frequency variants. To determine whether rare or low-frequency coding variants are associated with LDL-C, we exome sequenced 2,005 individuals, including 554 individuals selected for extreme LDL-C (>98(th) or
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- 2014
19. Loss-of-Function Mutations in APOC3, Triglycerides, and Coronary Disease
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Stavroula Kanoni, Olle Melander, He Zhang, Omri Gottesman, Yingchang Lu, Nathan O. Stitziel, Caroline S. Fox, Stephen S. Rich, Ruth J. F. Loos, Jochen Kruppa, Bruce M. Psaty, Kathleen Stirrups, Jose M. Ordovas, Nora Franceschini, Majid Nikpay, Christie M. Ballantyne, Gonçalo R. Abecasis, Natalie R. van Zuydam, Dermot F. Reilly, Werner Koch, Kari E. North, George Hindy, Jacy R Crosby, Deborah N. Farlow, Nicholas G. D. Masca, Chenyi Xue, Leslie A. Lange, David R. Crosslin, Lisa W. Martin, Paul L. Auer, Oliviero Olivieri, Domenico Girelli, Russell P. Tracy, David Altshuler, Nicola Martinelli, Cristen J. Willer, Ron Do, Heribert Schunkert, Oddgeir L. Holmen, Gina M. Peloso, Sekar Kathiresan, James G. Wilson, Hyun Min Kang, Pier Angelica Merlini, Stefano Duga, Charles Kooperberg, Zheng-Zheng Tang, Gail P. Jarvik, Anuj Goel, Kristian Hveem, Alistair S. Hall, Thomas Meitinger, Marju Orho-Melander, Diego Ardissino, Themistocles L. Assimes, Rosanna Asselta, Elizabeth K. Speliotes, Franziska Degenhardt, Colin N. A. Palmer, Goo Jun, Youna Hu, Martin Farrall, Ruth McPherson, Stefan A. Escher, Mark A. DePristo, Namrata Gupta, Nicholas J. Wareham, L. Adrienne Cupples, Annette Peters, Danyu Lin, Raimund Erbel, Wu Yin, Jan-Håkan Jansson, Wolfgang Lieb, Hugh Watkins, Stacey Gabriel, Nilesh J. Samani, Inke R. König, Jennifer G. Robinson, Erwin P. Bottinger, Deborah A. Nickerson, Jeanette Erdmann, Christopher J. O'Donnell, Panos Deloukas, Eric Boerwinkle, Alexander P. Reiner, and Erbel, Raimund (Beitragende*r)
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medicine.medical_specialty ,Nonsense mutation ,Medizin ,Endocrinology and Diabetes ,medicine.disease_cause ,Article ,Internal medicine ,Genotype ,Medicine ,Missense mutation ,Cardiac and Cardiovascular Systems ,Exome ,triglycerides ,Exome sequencing ,Genetics ,Mutation ,Apolipoprotein C-III ,apolipoproteins ,apo C3 ,business.industry ,General Medicine ,Odds ratio ,Endocrinology ,Apolipoprotein C3 ,coronary artery disease ,business - Abstract
Background Plasma triglyceride levels are heritable and are correlated with the risk of coronary heart disease. Sequencing of the protein-coding regions of the human genome (the exome) has the potential to identify rare mutations that have a large effect on phenotype. Methods We sequenced the protein-coding regions of 18,666 genes in each of 3734 participants of European or African ancestry in the Exome Sequencing Project. We conducted tests to determine whether rare mutations in coding sequence, individually or in aggregate within a gene, were associated with plasma triglyceride levels. For mutations associated with triglyceride levels, we subsequently evaluated their association with the risk of coronary heart disease in 110,970 persons. Results An aggregate of rare mutations in the gene encoding apolipoprotein C3 (APOC3) was associated with lower plasma triglyceride levels. Among the four mutations that drove this result, three were loss-of-function mutations: a nonsense mutation (R19X) and two splice-site mutations (IVS2+1G -> A and IVS3+1G -> T). The fourth was a missense mutation (A43T). Approximately 1 in 150 persons in the study was a heterozygous carrier of at least one of these four mutations. Triglyceride levels in the carriers were 39% lower than levels in noncarriers (P
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- 2014
20. Accurate local-ancestry inference in exome-sequenced admixed individuals via off-target sequence reads
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Gonçalo R. Abecasis, Xiaowei Zhan, Youna Hu, Cristen J. Willer, and Hyun Min Kang
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Genotype ,Population ,Genome-wide association study ,Computational biology ,Biology ,Empirical Research ,Linkage Disequilibrium ,Article ,Genetics ,Humans ,Genetics(clinical) ,Computer Simulation ,Exome ,1000 Genomes Project ,education ,Genotyping ,Genetics (clinical) ,Exome sequencing ,Genetic Association Studies ,Genetic association ,Oligonucleotide Array Sequence Analysis ,education.field_of_study ,Models, Genetic ,Genome, Human ,Chromosome Mapping ,Sequence Analysis, DNA ,Markov Chains ,Black or African American ,Genetics, Population ,Human genome ,Algorithms ,Software - Abstract
Estimates of the ancestry of specific chromosomal regions in admixed individuals are useful for studies of human evolutionary history and for genetic association studies. Previously, this ancestry inference relied on high-quality genotypes from genome-wide association study (GWAS) arrays. These high-quality genotypes are not always available when samples are exome sequenced, and exome sequencing is the strategy of choice for many ongoing genetic studies. Here we show that off-target reads generated during exome-sequencing experiments can be combined with on-target reads to accurately estimate the ancestry of each chromosomal segment in an admixed individual. To reconstruct local ancestry, our method SEQMIX models aligned bases directly instead of relying on hard genotype calls. We evaluate the accuracy of our method through simulations and analysis of samples sequenced by the 1000 Genomes Project and the NHLBI Grand Opportunity Exome Sequencing Project. In African Americans, we show that local-ancestry estimates derived by our method are very similar to those derived with Illumina’s Omni 2.5M genotyping array and much improved in relation to estimates that use only exome genotypes and ignore off-target sequencing reads. Software implementing this method, SEQMIX, can be applied to analysis of human population history or used for genetic association studies in admixed individuals.
- Published
- 2013
21. Effect of High-Temperature Paraffin Impregnation on the Properties of the Amorphous Cellulose Region Based on Molecular Dynamics Simulation
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Zening Qu, Wei Wang, Youna Hua, and Shilong Cang
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paraffin heat treatment ,wood cellulose ,molecular dynamics ,mechanical properties ,Plant ecology ,QK900-989 - Abstract
A paraffin–cellulose composite model was created using Materials Studio software, establishing a cellulose chain with a polymerization degree of 20 and paraffin molecules. A theoretical foundation for the research of wood heat treatment was established by explaining the changes in macroscopic qualities, such as mechanical properties, water absorption, etc., from a microscopic point of view. The model tended to a stable state with lower energy through geometric optimization and kinetic relaxation. The dynamics simulation was run based on this condition at a total of five different temperatures: 100 °C, 150 °C, 170 °C, 190 °C, and 210 °C. The energy balance, paraffin molecular diffusion coefficients, cell parameters and densities, hydrogen bonding numbers and mechanical parameters of the paraffin–cellulose composite model were analyzed. The results demonstrated that the paraffin diffusion range increased with temperature, and the paraffin diffusion coefficient was greatest at 210 °C, which also resulted in the maximum cell volume, the lowest density, and the lowest water absorption at this temperature. On the other hand, the paraffin–cellulose hybrid model had the most hydrogen bonds and the most stable system at 100 °C. The mechanical properties of the amorphous cellulose region of wood are influenced by temperature. According to the calculation of Lamé constants, with the system’s temperature rise, Young’s modulus (E) and shear modulus (G) were maximum at 100 °C, indicating the wood’s optimal toughness and plasticity. Poisson’s ratio and K/G values were largest at 210 °C, indicating the optimal toughness and plasticity of wood. The thermal modification of wood under different conditions can not only retain its natural advantages, but also improve its own performance, expand the application range of wood, and increase the utilization rate of wood. Therefore, the appropriate temperature and other conditions can be selected according to the actual needs of the wood heat treatment, which has significant practical significance for the study of wood heat treatment.
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- 2023
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22. Fluid overload at initiation of renal replacement therapy is associated with lack of renal recovery in patients with acute kidney injury
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Mallika Kommareddi, Michael Heung, Akinlolu O. Ojo, Youna Hu, Dawn F. Wolfgram, and Peter X.-K. Song
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Adult ,Male ,medicine.medical_specialty ,Time Factors ,medicine.medical_treatment ,Renal function ,urologic and male genital diseases ,Internal medicine ,medicine ,Humans ,Renal replacement therapy ,Dialysis ,Acute tubular necrosis ,Aged ,Retrospective Studies ,Transplantation ,Kidney ,business.industry ,Hazard ratio ,Acute kidney injury ,Water Intoxication ,Original Articles ,Acute Kidney Injury ,Middle Aged ,medicine.disease ,female genital diseases and pregnancy complications ,Surgery ,Body Fluids ,Renal Replacement Therapy ,Survival Rate ,medicine.anatomical_structure ,Nephrology ,Fluid Therapy ,Female ,Hemodialysis ,business - Abstract
Background. Patients with acute kidney injury (AKI) requiring initiation of renal replacement therapy (RRT) have poor short- and long-term outcomes, including the development of dialysis dependence. Currently, little is known about what factors may predict renal recovery in this population. Methods. We conducted a single-center, retrospective analysis of 170 hospitalized adult patients with AKI attributed to acute tubular necrosis who required inpatient initiation of RRT. Data collection included patient characteristics, laboratory data, details of hospital course and degree of fluid overload at RRT initiation. The primary outcome was recovery of renal function to dialysis independence. Results. Within 1 year of RRT initiation, 35.9% (61/170) of patients reached the primary end point of renal recovery. The median (interquartile range) duration of RRT was 11 (3–33) days and 83.6% (51/61) recovered prior to hospital discharge. Recovering patients had significantly less fluid overload at the time of RRT initiation compared to non-recovering patients (3.5 versus 9.3%, P ¼ 0.004). In multivariate Cox proportional hazard regression analysis, a rise in percent fluid overload at dialysis initiation remained a significant negative predictor of renal recovery (hazard ratio 0.97, 95% confidence interval 0.95–1.00, P ¼ 0.024). Conclusions. In patients with AKI, a higher degree of fluid overload at RRT initiation predicts worse renal recovery at 1 year. Clinical trials are needed to determine whether interventions targeting fluid overload may improve patient and renal outcomes.
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- 2011
23. The Effect of Heat Treatment and Acetylation on Formaldehyde Emission in Cellulose: A Molecular Dynamics Simulation Study
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Ning Li, Youna Hua, Jia Wang, Juncheng Li, and Wei Wang
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wood heat treatment ,acetylation ,formaldehyde emission ,molecular dynamics simulation ,Plant ecology ,QK900-989 - Abstract
Formaldehyde emission from cellulosic materials is an important consideration, especially for wood products, which are regulated by many countries in terms of legislation and may affect the health of users. In this study, molecular dynamics simulations were performed at different temperatures using two common wood-modification methods, heat treatment, and acetylation, and the diffusion coefficients of the models as well as the mechanical properties, were discussed. The results showed that the mean square displacement of the common heat treatment model was best at 493 K. The acetylated cellulose model at 483 K was able to achieve four times the diffusion coefficient of the common cellulose model, while the acetylated cellulose material would be weaker than the common heat-treated cellulose material in terms of mechanical properties. These findings provide some reference for formaldehyde pretreatment of wood products.
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- 2023
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24. GWAS of self-reported mosquito bite size, itch intensity and attractiveness to mosquitoes implicates immune-related predisposition loci.
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Jones, Amy V., Tilley, Mera, Gutteridge, Alex, Hyde, Craig, Nagle, Michael, Ziemek, Daniel, Gorman, Donal, Fauman, Eric B., Xing Chen, Miller, Melissa R., Chao Tian, Youna Hu, Hinds, David A., Cox, Peter, and Scollen, Serena
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- 2017
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25. Genome-wide association analysis of pain severity in dysmenorrhea identifies association at chromosome 1p13.2, near the nerve growth factor locus.
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Jones, Amy V., Hockley, James R. F., Hyde, Craig, Gorman, Donal, Sredic-Rhodes, Ana, Bilsland, James, McMurray, Gordon, Furlotte, Nicholas A., Youna Hu, Hinds, David A., Cox, Peter J., Scollen, Serena, and Hu, Youna
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- 2016
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26. Identification of a rare coding variant in complement 3 associated with age-related macular degeneration
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John R. Heckenlively, Stuart Cantsilieris, Rinki Ratnapriya, Emily Y. Chew, Yvette P. Conley, Albert Hofman, Fred G. Pluthero, Lindsay A. Farrer, Gonçalo R. Abecasis, Jonathan L. Haines, Daniel C. Koboldt, Claudia N von Strachwitz, Richard K. Wilson, Mindy M. Zhang, Andrea J. Richardson, Yuri V. Sergeev, Goo Jun, Elaine R. Mardis, Felix Grassmann, Paul N. Baird, Lana M. Olson, Mohammad Othman, Catrina Fronick, Xiaowei Zhan, Hyun Min Kang, Matthew P. Johnson, Youna Hu, Matthew Brooks, Humma Shahid, Michael B. Gorin, Bernhard H. F. Weber, Michael L. Klein, Lucinda Fulton, Chaolong Wang, Alexis Boleda, David E. Larson, Valentina Cipriani, Dwight Stambolian, Christoph Licht, Hongrong Luo, Anthony T. Moore, Anand Swaroop, Ivana K. Kim, John R.W. Yates, Robert S. Fulton, Kang Zhang, Yingda Jiang, Denise J. Morgan, Margaret M. DeAngelis, Hong Ouyang, Kari Branham, Dajiang J. Liu, Daniel E. Weeks, Caroline C W Klaver, Gabriëlle H.S. Buitendijk, Cornelia M. van Duijn, Jennifer L. Bragg-Gresham, Margaret A. Pericak-Vance, Robyn H. Guymer, John Blangero, Ophthalmology, and Epidemiology
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Aging ,Genotype ,Complement Pathway, Alternative ,Genome-wide association study ,Biology ,Polymorphism, Single Nucleotide ,Complement factor B ,Article ,Macular Degeneration ,03 medical and health sciences ,0302 clinical medicine ,Gene Frequency ,Genetics ,medicine ,Gene ,Allele frequency ,030304 developmental biology ,0303 health sciences ,Genetic Variation ,Complement C3 ,Macular degeneration ,medicine.disease ,3. Good health ,Complement system ,Complement Factor H ,Factor H ,030221 ophthalmology & optometry ,Alternative complement pathway - Abstract
Macular degeneration is a common cause of blindness in the elderly. To identify rare coding variants associated with a large increase in risk of age-related macular degeneration (AMD), we sequenced 2,335 cases and 789 controls in 10 candidate loci (57 genes). To increase power, we augmented our control set with ancestry-matched exome-sequenced controls. An analysis of coding variation in 2,268 AMD cases and 2,268 ancestry-matched controls identified 2 large-effect rare variants: previously described p. Arg1210Cys encoded in the CFH gene (case frequency (f(case)) = 0.51%; control frequency (f(control)) = 0.02%; odds ratio (OR) = 23.11) and newly identified p. Lys155Gln encoded in the C3 gene (f(case) = 1.06%; f(control) = 0.39%; OR = 2.68). The variants suggest decreased inhibition of C3 by complement factor H, resulting in increased activation of the alternative complement pathway, as a key component of disease biology.
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- 2013
27. MEDICAL EXCLUSIONS TO SUCCESSFUL LIVING KIDNEY DONATION
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Akinlolu O. Ojo, P Song, Silas P. Norman, and Youna Hu
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Transplantation ,medicine.medical_specialty ,business.industry ,medicine ,Kidney donation ,Intensive care medicine ,business - Published
- 2008
28. The Benefits of Using Genetic Information to Design Prevention Trials
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Meena Kumari, Chun Fang Xu, Li Li, Nan Bing, Mika Kivimäki, Cathie Spino, Youna Hu, Gonçalo R. Abecasis, Philippa J. Talmud, John C. Whittaker, Hyun Min Kang, Kijoung Song, Margaret G. Ehm, Aroon D. Hingorani, Matthew R. Nelson, and Dawn M. Waterworth
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Research design ,medicine.medical_specialty ,Genotype ,Cost-Benefit Analysis ,Myocardial Infarction ,Genome-wide association study ,Disease ,Bioinformatics ,Article ,Statistical power ,Macular Degeneration ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Genetics ,medicine ,Humans ,Genetics(clinical) ,Genetic Testing ,Intensive care medicine ,Genetics (clinical) ,030304 developmental biology ,Genetic testing ,Clinical Trials as Topic ,0303 health sciences ,Models, Statistical ,medicine.diagnostic_test ,Cost–benefit analysis ,business.industry ,Genetic Variation ,Genetic architecture ,3. Good health ,Clinical trial ,Diabetes Mellitus, Type 1 ,Phenotype ,Diabetes Mellitus, Type 2 ,Research Design ,business ,030217 neurology & neurosurgery - Abstract
Clinical trials for preventative therapies are complex and costly endeavors focused on individuals likely to develop disease in a short time frame, randomizing them to treatment groups, and following them over time. In such trials, statistical power is governed by the rate of disease events in each group and cost is determined by randomization, treatment, and follow-up. Strategies that increase the rate of disease events by enrolling individuals with high risk of disease can significantly reduce study size, duration, and cost. Comprehensive study of common, complex diseases has resulted in a growing list of robustly associated genetic markers. Here, we evaluate the utility--in terms of trial size, duration, and cost--of enriching prevention trial samples by combining clinical information with genetic risk scores to identify individuals at greater risk of disease. We also describe a framework for utilizing genetic risk scores in these trials and evaluating the associated cost and time savings. With type 1 diabetes (T1D), type 2 diabetes (T2D), myocardial infarction (MI), and advanced age-related macular degeneration (AMD) as examples, we illustrate the potential and limitations of using genetic data for prevention trial design. We illustrate settings where incorporating genetic information could reduce trial cost or duration considerably, as well as settings where potential savings are negligible. Results are strongly dependent on the genetic architecture of the disease, but we also show that these benefits should increase as the list of robustly associated markers for each disease grows and as large samples of genotyped individuals become available.
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29. Whole-Exome Sequencing of 2,000 Danish Individuals and the Role of Rare Coding Variants in Type 2 Diabetes
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Michael DeGiorgio, Torben Hansen, Rasmus Nielsen, Torben Jørgensen, Youna Hu, Niels Grarup, Annelli Sandbæk, Tune H. Pers, Yingrui Li, Kristoffer Kiil, Ingileif Hallgrimsdottir, Qibin Li, Thomas Sparsø, Kirk E. Lohmueller, Karina Banasik, Søren Brunak, Ehm A. Andersson, Jun Wang, Gaston Sanchez, Nikolaj T. Krarup, Thorfinn Sand Korneliussen, Karsten Kristiansen, Torsten Lauritzen, Tuomas O. Kilpeläinen, Oluf Pedersen, and Anders Albrechtsen
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Nonsynonymous substitution ,Genotype ,Denmark ,European Continental Ancestry Group ,Type 2 diabetes ,Biology ,Polymorphism, Single Nucleotide ,White People ,Article ,Danish ,03 medical and health sciences ,Open Reading Frames ,0302 clinical medicine ,Genetic variation ,medicine ,Genetics ,Humans ,Genetics(clinical) ,Exome ,Gene ,Genetics (clinical) ,Exome sequencing ,Genetic Association Studies ,030304 developmental biology ,0303 health sciences ,Models, Statistical ,030305 genetics & heredity ,Computational Biology ,Genetic Variation ,High-Throughput Nucleotide Sequencing ,Heritability ,medicine.disease ,language.human_language ,Human genetics ,3. Good health ,Diabetes Mellitus, Type 2 ,language ,Erratum ,030217 neurology & neurosurgery ,Coding (social sciences) ,Common disease-common variant - Abstract
It has been hypothesized that, in aggregate, rare variants in coding regions of genes explain a substantial fraction of the heritability of common diseases. We sequenced the exomes of 1,000 Danish cases with common forms of type 2 diabetes (including body mass index > 27.5 kg/m2 and hypertension) and 1,000 healthy controls to an average depth of 56×. Our simulations suggest that our study had the statistical power to detect at least one causal gene (a gene containing causal mutations) if the heritability of these common diseases was explained by rare variants in the coding regions of a limited number of genes. We applied a series of gene-based tests to detect such susceptibility genes. However, no gene showed a significant association with disease risk after we corrected for the number of genes analyzed. Thus, we could reject a model for the genetic architecture of type 2 diabetes where rare nonsynonymous variants clustered in a modest number of genes (fewer than 20) are responsible for the majority of disease risk.
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