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1.
J Nanosci Nanotechnol ; 20(4): 2573-2577, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31492278

RESUMO

The reliability of solder joints, which is affected largely by the interfacial intermetallic compounds layer, is of great importance to the performance of electronic devices. In this paper, a novel composite solder with Mo nanoparticles doped in Sn3.0Ag0.5Cu solder was prepared. Solder/Cu joints were prepared using Sn3.0Ag0.5Cu solder or Mo nanoparticles reinforced solder with Cu substrates. The effect of the nanoparticles on the growth of intermetallic compounds during isothermal aging was investigated. It was found that the addition of Mo nanoparticle markedly suppressed the increase in thickness of the interfacial intermetallic compounds layer during isothermal aging. The atomic diffusion coefficients during isothermal aging in Sn3.0Ag0.5Cu solder and in the novel doped solder were determined experimentally. Mo nanoparticles were found to decrease the diffusion coefficient in the composite solder. The high specific surface area of the nanoparticles makes them easily adsorbed and hinders the diffusion of Sn and Cu atoms. This is consistent with an increase in the diffusion activation energy due to the addition of Mo nanoparticles in Sn3.0Ag0.5Cu solder.

2.
Opt Lett ; 44(21): 5181-5184, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31674961

RESUMO

We experimentally demonstrate turbulence effect mitigation in a 100-m round-trip orbital-angular-momentum (OAM)-multiplexed free-space optical communication link between a ground transmitter and a ground receiver via a retro-reflecting hovering unmanned aerial vehicle (UAV) using multiple-input-multiple-output (MIMO) equalization. In our demonstration, two OAM beams at 1550 nm are transmitted to the UAV through emulated atmospheric turbulence, each carrying a 20-Gbit/s signal. 2×2 MIMO equalization is used to mitigate turbulence-induced crosstalk between the two OAM channels. Bit error rates below the 7% overhead forward error correction limit of 3.8×10-3 are achieved for both channels.

3.
JCI Insight ; 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31689243

RESUMO

The HER2-specific monoclonal antibody (mAb), Trastuzumab, has been the mainstay of therapy for HER2+ breast cancers (BC) for ~20 years. However, its therapeutic mechanism of action (MOA) remains unclear, with antitumor responses to Trastuzumab remaining heterologous and metastatic HER2+ BC remaining incurable. Consequently, understanding its MOA could enable rational strategies to enhance its efficacy. Using both novel murine and human versions of Trastuzumab, we found its antitumor activity dependent on Fcγ-Receptor stimulation of tumor-associated-macrophages (TAM) and Antibody-Dependent-Cellular-Phagocytosis (ADCP), but not cytotoxicity (ADCC). Trastuzumab also stimulated TAM activation and expansion, but did not require adaptive immunity, natural killer cells, and/or neutrophils. Moreover, inhibition of the innate immune ADCP checkpoint, CD47, significantly enhanced Trastuzumab-mediated ADCP, TAM expansion and activation, resulting in the emergence of a unique hyper-phagocytic macrophage population, improved antitumor responses and prolonged survival. In addition, we found tumor-associated CD47 expression was inversely associated with survival in HER2+ BC patients and that human HER2+ BC xenografts treated with Trastuzumab+CD47 inhibition underwent complete tumor regression. Collectively, our study identifies Trastuzumab-mediated ADCP as a significant antitumor MOA that may be clinically enabled by CD47 blockade to augment therapeutic efficacy.

4.
J Craniofac Surg ; 30(8): e776-e780, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31689739

RESUMO

OBJECTIVE: Granulocyte colony-stimulating factor (G-CSF) is the critical regulator of the proliferation, differentiation, and survival of granulocytes. Recently, it has been shown that G-CSF can adversely affect bone health in both animal models and patients. Here, the authors aimed to investigate whether G-CSF could inhibit the growth of osteoblasts and osteocytes by regulating nitric oxide. METHODS: The C57BL/6 mice were divided into the control group, G-CSF treatment group and recovery group (G-CSF+L-NAME). The morphology of femurs was assessed by histology and immunohistochemistry. The expression of apoptosis-related molecules in femurs was detected by immunohistochemistry and quantitative RT-PCR, respectively. To examine if neutrophil-secreted factors can induce apoptosis in osteoblasts, Gr1-positive (Gr1+) neutrophils from the bone marrow of wild-type mice were sorted and co-cultured with MC3T3 pre-osteoblasts for 2 days. RESULTS: The number of osteoblasts and newly embedding osteocytes significantly decreased and markers related to osteoblasts and osteocytes were downregulated in the G-CSF treatment compared to the control group. Moreover, G-CSF treatment did not change proliferation markers but induced apoptosis in osteoblast-lineage cells. The combined treatment of mice with G-CSF and a nitric oxide inhibitor partially restored the number of osteoblasts and osteocyte parameters. CONCLUSIONS: The G-CSF can inhibit osteoblasts and osteocytes by upregulating nitric oxide.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31669095

RESUMO

BACKGROUND: Clinical and epidemiological studies have shown that obesity is associated with asthma and that these associations differ by asthma subtypes. Little is known about the shared genetic components between obesity and asthma. OBJECTIVE: To identify shared genetic associations between obesity-related traits and asthma subtypes in adults. METHODS: A cross-trait genome-wide association study (GWAS) was performed using 457,822 individuals of European ancestry from the UK Biobank. Experimental evidence to support the role of genes significantly associated with both obesity-related traits and asthma via GWAS was sought using results from obese vs. lean mouse RNA-seq and RT-PCR experiments. RESULTS: We found a substantial positive genetic correlation between BMI and later-onset asthma defined by asthma age of onset at 16 years of age or older (Rg =0.25, P=9.56×10-22). Mendelian Randomization analysis provided strong evidence in support of BMI causally increasing the risk of asthma. Cross-trait meta-analysis identified 34 shared loci among 3 obesity-related traits and 2 asthma subtypes. GWAS functional analyses identified potential causal relationships between the shared loci and GTEx tissue eQTLs, shared immune- and cell differentiation-related pathways between obesity and asthma. Finally, RNA-seq data from lungs of obese versus control mice found that two genes (ACOXL and MYL6) from the cross-trait meta-analysis were differentially expressed, and these findings were validated by RT-PCR in an independent set of mice. CONCLUSIONS: Our work identified shared genetic components between obesity-related traits and specific asthma subtypes, reinforcing the hypothesis that obesity causally increases the risk of asthma, and identifying molecular pathways that may underlie both obesity and asthma.

6.
J Nutr Biochem ; 74: 108246, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31671360

RESUMO

The risk of overweight or obesity in association with early exposure of antibiotics remains an important public issue for health-care of children. Low-dose antibiotics (LDA) have been widely used to enhance growth rate of pigs, providing a good animal model to study the underlying mechanism. In present study, 28 female piglets, weaned at 21 d, were randomly classified into two groups, receiving either a control diet or a diet supplemented with LDA for 4 weeks. The total bacterial load and intestinal microbiota were determined by qPCR and 16S rRNA amplicon sequencing. UPLC-QTRAP-MS/MS and RNA-seq were further used to determine the colonic SCFAs and transcriptomes. Results showed that LDA significantly increased growth rate and food intake. The F/B index, Methanosphaera species, and the pathway of "carbohydrate metabolism" were improved by LDA exposure, indicating the better carbohydrate degradation and energy utilization. Furthermore, correlation analysis indicated the microbial community contributing to SCFAs production was enriched upon LDA exposure, associating with increased concentrations of short-chain and branched-chain fatty acids (caproate, 2-methyl butyrate and 4-methyl valerate). A multivariate linear fitting model analysis highlighted that caproate was positively correlated with two genera (Faecalibacterium and Allisonella) and four differentially expressed genes (ZNF134, TBX5, NEU4 and SEMA6D), which were all significantly increased upon LDA exposure. Collectively, our study indicates that the growth-promoting effect of LDA exposure in early life is associated with the shifts of colonic microbiota to increase utilization of carbohydrates and energy, enhanced SCFAs production and colonic functions.

7.
Photochem Photobiol ; 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31574562

RESUMO

DVDMS-2 is a novel candidate for photodynamic therapy of tumors. The purpose of the present study was to assess the distribution and elimination of DVDMS-2 in mice bearing hepatoma 22 tumors. DVDMS-2 (1, 2 and 4 mg kg-1 ) was injected intravenously into the mice, extracted from biological tissues and quantified using a fluorescence assay. The data obtained were processed with WinNonlin pharmacokinetic software. The fluorescence assay established for DVDMS-2 quantification was a rapid, reproducible, sensitive and specific method with good linearity. The pharmacokinetics of DVDMS-2 in tumor-bearing mice conformed to a two-compartment model. DVDMS-2 accumulated in tumor tissue to a greater extent than adjacent tissues (skin, muscle) and sustained a relatively high-level concentration 12 to 24 h following administration, which may be the optimal treatment time point. In conclusion, DVDMS-2 selectively accumulated in tumor tissue and was eliminated at a rapid rate in tumor-bearing mice, suggesting that DVDMS-2 may have few side effects, including skin phototoxicity. The present study established the pharmacokinetic characteristics of DVDMS-2, which may be beneficial in future clinical study.

8.
Chemosphere ; 241: 125024, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31604191

RESUMO

Emission of reactive nitrogen species has a major impact on atmospheric chemistry, ecosystem and human health. The origin and formation mechanisms of wet-deposited nitrate are not well understood in Southeast Asia (SEA). In this study, we measured stable isotopes of nitrate (δ15N and δ18O) and chemical compositions of daily rainwater from May 2015 to July 2017 in Singapore. Our results showed that δ15N-NO3- and δ18O-NO3- varied seasonally with higher values during the Inter-monsoon period (April-May and October-November) than during Northeast (December-March) and Southwest monsoon (June-September). Bayesian mixing modeling, which took account of the isotope fractionation, indicated that traffic emission (47 ±â€¯32%) and lightning (19 ±â€¯20%) contributed the most to NO3- with increased traffic contribution (55 ±â€¯37%) in the Northeast monsoon and lightning (24 ±â€¯23%) during the Inter-monsoon period. Biomass burning and coal combustion, likely from transboundary transport, contributed ∼25% of nitrate in the rainwater. Monte Carlo simulation of δ18O-NO3- indicated that oxidation process by hydroxyl radical contributed 65 ±â€¯14% of NO3-, with the rest from hydrolysis of N2O5. Wind speed had large effect on δ18O-NO3- variations in the atmosphere with more involvement of hydroxyl radical reactions when wind speed increased. Our study highlights the key role of isotopic fractionation in nitrate source apportionment, and the influence of meteorological conditions on nitrate formation processes in SEA.

9.
Eur Respir J ; 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31619474

RESUMO

Epidemiological studies demonstrate an association between asthma and mental health disorders, although little is known about the shared genetics and causality of this association. Thus, we aim to investigate shared genetic and the causal link between asthma and mental health disorders.We conducted a large-scale genome-wide cross-trait association study to investigate genetic overlap between asthma from UK Biobank and 8 mental health disorders from Psychiatric Genomics Consortium, including: attention deficit hyperactivity disorder (ADHD), anxiety disorder (ANX), autism spectrum disorder, bipolar disorder, eating disorder, major depressive disorder (MDD), posttraumatic stress disorder, and schizophrenia, with a sample size of 7556 to 446 032.In the single trait genome-wide association analysis, we replicated 130 and discovered 31 novel independent loci that are associated with asthma. We identified that ADHD, ANX and MDD have strong genetic correlation with asthma at the genome-wide level. Cross-trait meta-analysis identified 7 loci jointly associated with asthma and ADHD, 1 loci with asthma and ANX and 10 loci with asthma and MDD. Functional analysis revealed that the identified variants regulated gene expression in major tissues belonging to exocrine/endocrine, digestive, respiratory and hemic/immune system. Mendelian randomisation analyses suggested that ADHD and MDD (including 6.7% samples overlap with asthma) might increase the risk of asthma.This large-scale genome-wide cross-trait analysis identified shared genetics and potential causal links between asthma and three mental health disorders (ADHD, ANX, and MDD). Such shared genetics implicate potential new biological functions that are in common among them.

10.
J Mater Sci Mater Med ; 30(10): 112, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31583472

RESUMO

Co-Cr-Mo alloys have been widely used in hip implants due to their good corrosion resistance and good wear resistance. However, complaint is still raising due to infection and inflammation. The addition of Cu has been proven to be an effective way to develop a new kind of Co-based alloy with good antibacterial properties. In this paper, the effect of heat treatment on the corrosion property, the tribology property and the antibacterial property of Cu containing Co-based alloys were investigated in detail. The microstructure observation showed that the as-cast alloys mainly consisted of a dendritic matrix with carbide dispersion at grain boundaries and a fine Cu-rich phase in the matrix and at the carbide/matrix interface. The carbide precipitates and the distribution of Cu phases affected significantly the friction coefficient and wear resistance of Co-xCu alloy. Annealing at 1060 °C/24 h promoted the precipitation of carbide and in turn increased the hardness and wear resistance markedly. Heat treatments, including annealing, solid solution and ageing treatment, enhanced the corrosion resistance of Co-xCu alloy without reduction in antibacterial properties. However, the addition of Cu increased the corrosion resistance and antibacterial properties but reduced the wear resistance especially at high Cu content.

12.
J Cell Mol Med ; 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31650683

RESUMO

Inflammation is as an important component of intestinal tumorigenesis. The activation of Toll-like receptor 4 (TLR4) signalling promotes inflammation in colitis of mice, but the role of TLR4 in intestinal tumorigenesis is not yet clear. About 80%-90% of colorectal tumours contain inactivating mutations in the adenomatous polyposis coli (Apc) tumour suppressor, and intestinal adenoma carcinogenesis in familial adenomatous polyposis (FAP) is also closely related to the germline mutations in Apc. The ApcMin/+ (multiple intestinal neoplasia) model mouse is a well-utilized model of FAP, an inherited form of intestinal cancer. In this study, ApcMin/+ intestinal adenoma mice were generated on TLR4-sufficient and TLR4-deficient backgrounds to investigate the carcinogenic effect of TLR4 in mouse gut by comparing mice survival, peripheral blood cells, bone marrow haematopoietic precursor cells and numbers of polyps in the guts of ApcMin/+ WT and ApcMin/+ TLR4-/- mice. The results revealed that TLR4 had a critical role in promoting spontaneous intestinal tumorigenesis. Significant differential genes were screened out by the high-throughput RNA-Seq method. After combining these results with KEGG enrichment data, it was determined that TLR4 might promote intestinal tumorigenesis by activating cytokine-cytokine receptor interaction and pathways in cancer signalling pathways. After a series of validation experiments for the concerned genes, it was found that IL6, GM-CSF (CSF2), IL11, CCL3, S100A8 and S100A9 were significantly decreased in gut tumours of ApcMin/+ TLR4-/- mice compared with ApcMin/+ WT mice. In the functional study of core down-regulation factors, it was found that IL6, GM-CSF, IL11, CCL3 and S100A8/9 increased the viability of colon cancer cell lines and decreased the apoptosis rate of colon cancer cells with irradiation and chemical treatment.

13.
Nat Commun ; 10(1): 4664, 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31604935

RESUMO

Signal transduction systems enable organisms to monitor their external environments and accordingly adjust the cellular processes. In mast cells, the second messenger Ap4A binds to the histidine triad nucleotide-binding protein 1 (HINT1), disrupts its interaction with the microphthalmia-associated transcription factor (MITF), and eventually activates the transcription of genes downstream of MITF in response to immunostimulation. How the HINT1 protein recognizes and is regulated by Ap4A remain unclear. Here, using eight crystal structures, biochemical experiments, negative stain electron microscopy, and cellular experiments, we report that Ap4A specifically polymerizes HINT1 in solution and in activated rat basophilic leukemia cells. The polymerization interface overlaps with the area on HINT1 for MITF interaction, suggesting a possible competitive mechanism to release MITF for transcriptional activation. The mechanism depends precisely on the length of the phosphodiester linkage of Ap4A. These results highlight a direct polymerization signaling mechanism by the second messenger.

14.
Phys Rev E ; 100(3-1): 032206, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31639972

RESUMO

We investigate the collective response of an ensemble of bistable oscillators to an external periodic signal, where the coupling strength between oscillators is diverse. We find that there exists an optimal level of coupling diversity, at which the collective response of the system can be largely improved, i.e., resonance induced by coupling diversity. We also observe that the system splits into three oscillation clusters when this resonance happens. We finally propose a reduced model based on the three oscillation clusters, which can well predict the collective response of the system.

15.
Curr Mol Med ; 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31595851

RESUMO

BACKGROUND: This study took the untreated OSAHS patients as the control group, exploring the influence of minimally invasive surgery treatment and CPAP therapy on OSAHS patients, subjective and objective performance, discussing their relationship, finding out the effect factor and providing a simple and practical evaluation of clinical efficacy. METHODS: Choose 90 OSAHS patients diagnosed in the Sleep Disorders Diagnosis and Treatment Center of Sichuan Province from May 2014 to May 2016,divide into surgery group, CPAP group and untreated group,then follow up in six month、1year、2year respectively. Compare three groups, physiological indicators, clinical symptoms, the degree of daytime sleepiness and quality of life, evaluate the daytime sleepiness and quality of life changes before and after minimally invasive surgery and CPAP treatment, explore the subjective and objective efficacy of surgery and CPAP treatment. RESULTS: In the 90 patients,11(12.2%) had the hypertension, 2(2.2%) had the diabetes. The average AHI was 50.53±23.39 per hour,and the mean minimum oxygen saturation and mean oxygen saturation was 71.25±14.16%,90.13±5.90% respectively; There were statistical significant in mouth breathing、morning throat、daytime sleepiness in surgery group at 0.5 year and 1year; In CPAP group,there were statistical significant in mouth breathing、morning throat、daytime sleepiness at 0.5 year、1year and 2year, there was statistical significant in memory loss at 1year and 2year, there was statistical significant in frequent nocturia at 1year; The ESS value in surgery group decreased at 0.5y and 1y,but increased at 2year.The situation was the same in total points and each dimension of SF-36; The delta values of ESS among three groups had statistical significant at 0.5year、1year and 2year, and CPAP group changed the most, followed by surgery group and healthy education group. CONCLUSIONS: All the minimally invasive surgery、CPAP therapy and healthy education can improve the daytime sleepiness and quality of life, CPAP therapy changed the most, followed by minimally invasive surgery and healthy education. But the treatment of OSAHS should be comprehensive.

16.
Clin Lab ; 65(10)2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31625349

RESUMO

BACKGROUND: The pneumonia severity index (PSI) scoring system is one of the tools used to evaluate and predict the prognosis of patients with community-acquired pneumonia (CAP). Although PSI has been widely used in clinical studies of pneumonia, it is still rare to combine it with blood indexes to predict the prognosis of pneumonia. Neutrophil-to-lymphocyte ratio (NLR) is a promising candidate predictor of mortality in CAP patients. The aim of this study was to investigate the efficacy of pneumonia severity index combined with NLR in predicting 30-day mortality in CAP patients. METHODS: We conducted a retrospective study. We analyzed data on 400 non-immune individuals over the age of 18 in this study. All patients received blood routine measurement and PSI score calculation after admission. The primary outcome measures were mortality and survival in CAP patients. The sensitivity and specificity of PSI score, NLR, and the combination of PSI score and NLR in predicting 30-day mortality were assessed using the subject operating characteristic curve (ROC). RESULTS: Data from 400 patients were analyzed, in which the 30-day mortality was 10.5% (42/400). The AUC of NLR and PSI in predicting 30-day mortality of CAP patients were 0.81 (95% CI 0.73 - 0.89) and 0.94 (95% CI 0.90 - 0.98), respectively, with statistically significant differences (p = 0.00). The sensitivity and specificity of NLR were 0.80 and 0.7, respectively. The sensitivity and specificity of PSI were 0.78 and 0.94, respectively. The combined AUC of the two indicators for predicting death in CAP patients was 0.95 (95% CI 0.92 - 0.99), and the sensitivity and specificity were 0.85 and 0.94, respectively. CONCLUSIONS: Neutrophil-to-lymphocyte ratio improves the accuracy and sensitivity of the pneumonia severity index in predicting 30-day mortality of CAP patients.

17.
Forensic Sci Int Genet ; 44: 102171, 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31614309

RESUMO

Insertion/deletion polymorphisms (InDels) have attracted more and more attention of forensic researchers because of their low mutation rate and small amplicons. In the face of challenging forensic cases and degraded DNA, InDels break through the limitations of traditional STRs and provided a new direction for forensic identification. In this study, a multiplex panel consisting of 32 InDels and amelogenin was established and the InDels were selected with minimum allele frequencies (MAF) ≥ 0.4 in Chinese Han population based on the 1000 Genomes Project and published articles. The 32-plex InDels assay was evaluated using the southern Chinese Han population from Hubei province. All markers were proved to be highly polymorphic with an average observed heterozygosity (Hobs) of 0.4885. The combined power of discrimination (CPD) and the combined probability of paternity exclusion (CPE) were 0.999999999999966 and 0.9982, respectively. Further validation studies indicated that the 32-plex InDels assay was highly sensitive to DNA template amounts as low as 31.25 pg and was effective for degraded DNA. The obtained allele frequencies from this study were compared with published data of other populations.

18.
J Biomed Inform ; 100: 103318, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31655273

RESUMO

BACKGROUND: Manually curating standardized phenotypic concepts such as Human Phenotype Ontology (HPO) terms from narrative text in electronic health records (EHRs) is time consuming and error prone. Natural language processing (NLP) techniques can facilitate automated phenotype extraction and thus improve the efficiency of curating clinical phenotypes from clinical texts. While individual NLP systems can perform well for a single cohort, an ensemble-based method might shed light on increasing the portability of NLP pipelines across different cohorts. METHODS: We compared four NLP systems, MetaMapLite, MedLEE, ClinPhen and cTAKES, and four ensemble techniques, including intersection, union, majority-voting and machine learning, for extracting generic phenotypic concepts. We addressed two important research questions regarding automated phenotype recognition. First, we evaluated the performance of different approaches in identifying generic phenotypic concepts. Second, we compared the performance of different methods to identify patient-specific phenotypic concepts. To better quantify the effects caused by concept granularity differences on performance, we developed a novel evaluation metric that considered concept hierarchies and frequencies. Each of the approaches was evaluated on a gold standard set of clinical documents annotated by clinical experts. One dataset containing 1,609 concepts derived from 50 clinical notes from two different institutions was used in both evaluations, and an additional dataset of 608 concepts derived from 50 case report abstracts obtained from PubMed was used for evaluation of identifying generic phenotypic concepts only. RESULTS: For generic phenotypic concept recognition, the top three performers in the NYP/CUIMC dataset are union ensemble (F1, 0.634), training-based ensemble (F1, 0.632), and majority vote-based ensemble (F1, 0.622). In the Mayo dataset, the top three are majority vote-based ensemble (F1, 0.642), cTAKES (F1, 0.615), and MedLEE (F1, 0.559). In the PubMed dataset, the top three are majority vote-based ensemble (F1, 0.719), training-based (F1, 0.696) and MetaMapLite (F1, 0.694). For identifying patient specific phenotypes, the top three performers in the NYP/CUIMC dataset are majority vote-based ensemble (F1, 0.610), MedLEE (F1, 0.609), and training-based ensemble (F1, 0.585). In the Mayo dataset, the top three are majority vote-based ensemble (F1, 0.604), cTAKES (F1, 0.531) and MedLEE (F1, 0.527). CONCLUSIONS: Our study demonstrates that ensembles of natural language processing can improve both generic phenotypic concept recognition and patient specific phenotypic concept identification over individual systems. Among the individual NLP systems, each individual system performed best when they were applied in the dataset that they were primary designed for. However, combining multiple NLP systems to create an ensemble can generally improve the performance. Specifically, the ensemble can increase the results reproducibility across different cohorts and tasks, and thus provide a more portable phenotyping solution compared to individual NLP systems.

19.
Artigo em Inglês | MEDLINE | ID: mdl-31586277

RESUMO

The alterations of the intestinal proteome were observed in intrauterine growth restriction (IUGR) piglets during early life by gel-based approaches. Nevertheless, how IUGR affects the intestinal membrane proteome during neonatal development remains unclear. Here, we applied the iTRAQ-based proteomics technology and biochemical analysis to investigate the impact of IUGR on the membrane proteome of the jejunal mucosa in the piglets. Three hundred sixty-one membrane proteins were screened by functional prediction. Among them, eight, five, and one differentially expressed membrane proteins were identified between IUGR and NBW piglets at day 0, day 7, and day 21 after birth, respectively. Differentially expressed membrane proteins (DEMPs) including F1SBL3, F1RRW8, F1S539, F1S2Z2, F1RIR2, F1RUF2 I3LP60, Q2EN79, and F1SIH8 were reduced while the relative abundance of I3L6A2, F1SCJ1, F1RI18, I3LRJ7, and F1RNN0 were increased in IUGR piglets than NBW piglets. From the aspects of function, F1RRW8, F1S539, F1S2Z2, and F1RIR2 are mainly associated with D2 dopamine receptor binding, transmembrane transport of small molecules, signal transduction, and translocation of GLUT4, respectively, and F1SIH8, I3LRJ7, and F1RNN0 are related to autophagy, metabolism of vitamins, and intracellular protein transport. Additionally, IUGR decreased the level of proteins (F1RRW8, Q2EN79, and F1RI18) that are involved in response to oxidative stress.

20.
J Biomed Inform ; 99: 103293, 2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31542521

RESUMO

BACKGROUND: Implementation of phenotype algorithms requires phenotype engineers to interpret human-readable algorithms and translate the description (text and flowcharts) into computable phenotypes - a process that can be labor intensive and error prone. To address the critical need for reducing the implementation efforts, it is important to develop portable algorithms. METHODS: We conducted a retrospective analysis of phenotype algorithms developed in the Electronic Medical Records and Genomics (eMERGE) network and identified common customization tasks required for implementation. A novel scoring system was developed to quantify portability from three aspects: Knowledge conversion, clause Interpretation, and Programming (KIP). Tasks were grouped into twenty representative categories. Experienced phenotype engineers were asked to estimate the average time spent on each category and evaluate time saving enabled by a common data model (CDM), specifically the Observational Medical Outcomes Partnership (OMOP) model, for each category. RESULTS: A total of 485 distinct clauses (phenotype criteria) were identified from 55 phenotype algorithms, corresponding to 1153 customization tasks. In addition to 25 non-phenotype-specific tasks, 46 tasks are related to interpretation, 613 tasks are related to knowledge conversion, and 469 tasks are related to programming. A score between 0 and 2 (0 for easy, 1 for moderate, and 2 for difficult portability) is assigned for each aspect, yielding a total KIP score range of 0 to 6. The average clause-wise KIP score to reflect portability is 1.37 ±â€¯1.38. Specifically, the average knowledge (K) score is 0.64 ±â€¯0.66, interpretation (I) score is 0.33 ±â€¯0.55, and programming (P) score is 0.40 ±â€¯0.64. 5% of the categories can be completed within one hour (median). 70% of the categories take from days to months to complete. The OMOP model can assist with vocabulary mapping tasks. CONCLUSION: This study presents firsthand knowledge of the substantial implementation efforts in phenotyping and introduces a novel metric (KIP) to measure portability of phenotype algorithms for quantifying such efforts across the eMERGE Network. Phenotype developers are encouraged to analyze and optimize the portability in regards to knowledge, interpretation and programming. CDMs can be used to improve the portability for some 'knowledge-oriented' tasks.

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