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1.
Contrast Media Mol Imaging ; 2022: 1350826, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36105445

RESUMO

Objective: To compare the value of a hepatectomy and hemangioma stripping on patients with giant hepatic hemangiomas. Methods: Seventy-four patients with giant hepatic hemangiomas were retrospectively analyzed from data collected from their hepatobiliary surgeries performed from June 2010 to June 2015 at the People's Hospital of Ningxia and the general hospital affiliated with Ningxia Medical University. The patients were divided into a hepatectomy group (37 patients) and a hemangioma-stripping group (37 patients). Conditions of each group were compared before and after surgery and comprised of surgery duration, intraoperative blood loss, blood transfusion, duration of hepatic blood occlusion, and hospital stay. Any complications after surgery, such as pleural effusions, bile leakage, and abdominal hemorrhage, were also observed. Results: In the hemangioma-stripping group, the surgery time was 2.38 ± 0.93 h, intraoperative blood loss was 889.19 ± 756.37, blood transfusion amount was 723.78 ± 801.14, the duration of hepatic blood occlusion 26.84 ± 17.30 min, and hospital stay was 16.19 ± 5.01 d. In the hepatectomy group, surgery time was 3.26 ± 1.16 h, intraoperative blood loss was 1551.35 ± 1755.88 mL blood transfusion amount was 1693.24 ± 2117.72 mL, duration of hepatic blood occlusion was 26.84 ± 17.30 min, and hospital stay was 16.19 ± 5.01 d. The difference between the groups was statistically significant (P < 0.05). The pleural effusion incident rate in the former group was lower than that of the latter group, and the difference was statistically significant. Conclusions: Hemangiomas stripping is an effective method by which to cure hepatic hemangioma, with the advantages being a relatively easy surgery with less patient trauma, rapid recovery, and fewer complications. This method should be used more often in clinical settings.


Assuntos
Hemangioma , Neoplasias Hepáticas , Perda Sanguínea Cirúrgica , Hemangioma/cirurgia , Hepatectomia/métodos , Humanos , Neoplasias Hepáticas/cirurgia , Estudos Retrospectivos
2.
Stat Commun Infect Dis ; 14(1): 20210001, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35880974

RESUMO

Objectives: Characterizing features of the viral rebound trajectories and identifying host, virological, and immunological factors that are predictive of the viral rebound trajectories are central to HIV cure research. We investigate if key features of HIV viral decay and CD4 trajectories during antiretroviral therapy (ART) are associated with characteristics of HIV viral rebound following ART interruption. Methods: Nonlinear mixed effect (NLME) models are used to model viral load trajectories before and following ART interruption, incorporating left censoring due to lower detection limits of viral load assays. A stochastic approximation EM (SAEM) algorithm is used for parameter estimation and inference. To circumvent the computational intensity associated with maximizing the joint likelihood, we propose an easy-to-implement three-step method. Results: We evaluate the performance of the proposed method through simulation studies and apply it to data from the Zurich Primary HIV Infection Study. We find that some key features of viral load during ART (e.g., viral decay rate) are significantly associated with important characteristics of viral rebound following ART interruption (e.g., viral set point). Conclusions: The proposed three-step method works well. We have shown that key features of viral decay during ART may be associated with important features of viral rebound following ART interruption.

3.
J Healthc Eng ; 2022: 8508943, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35469227

RESUMO

To evaluate the efficacy and safety of endoscopic retrograde cholangiopancreatography (ERCP) in the treatment of patients with symptomatic pancreas divisum (PD) and to discuss the possible risk factors of endoscopic reintervention for symptomatic PD. A total of 50 patients with symptomatic PD who underwent ERCP from January 2010 to December 2019 were finally brought into study. All patients were divided into the nonage and the adult group according to their ages. Meanwhile, all patients were also divided into the intervention and the reintervention group according to times of ERCP. The long-term outcome of each patient was collected during the follow-up by phone call. The total success rate of ERCP was 94.7% (89/93), and the effective rate of first ERCP was 58% (29/50). There were no statistical differences on the outcomes of ERCP treatment between the adult and nonage group. There were 17 patients with complete pancreas divisum and 19 patients with chronic pancreatitis in the reintervention group, which were more than 6 patients and 8 patients in the intervention group (P < 0.05). In bivariate regression analysis, chronic pancreatitis and complete pancreas divisum might be significant risk factors for endoscopic reintervention for patients with symptomatic PD (OR, 8.010, 95% CI, 1.483-43.276, P=0.016; OR, 8.869, 95% CI, 1.450-54.254, P=0.018, respectively). ERCP in treating adult and nonage patients with symptomatic PD are effective and safe. But, many patients may need endoscopic reintervention. Complete pancreas divisum and chronic pancreatitis may be risk factors of ERCP reintervention for patients with symptomatic PD.


Assuntos
Pâncreas , Pancreatite Crônica , Adulto , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Humanos , Pâncreas/diagnóstico por imagem , Pâncreas/cirurgia , Pancreatite Crônica/etiologia , Pancreatite Crônica/cirurgia
4.
Geriatr Gerontol Int ; 22(1): 50-55, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34850514

RESUMO

AIMS: This study aimed to explore the safety and efficacy of endoscopic retrograde cholangiopancreatography (ERCP) in patients over 90 years of age. METHODS: The study included 176 patients aged over 85 years who received their ERCP from February 2002 to January 2021. In the case group (super-elderly group), 44 patients were 90 years old or above. In the control group (younger group), there were 132 patients aged 85-89 years. The control group was matched according to patient gender and the same indications of ERCP at a 1:3 ratio. Logistic regression models were employed to evaluate all complications. RESULTS: The case group had higher acute physiology and chronic health evaluation scoring system (APACHE-II) scores and rate of hypoalbuminemia. APACHE-II scores (≥6 or 7) were significantly more common in the case group. The rates of technical success and complete success in the case group were 100% and 100% respectively, which were similar to the rates in the control group, namely a technical success rate of 98.5% and a complete success rate of 98.5%. The rate of complication in the case group was 9.1%, which was slightly lower than that of the control group (15.2%, P > 0.05). ERCP-related death occurred in one patient in the control group, who had malignant biliary obstruction and died from cholangitis. There was no significant difference in the incidence of complications such as pancreatitis, hemorrhage, and infection between the two groups. In the multivariate analysis, the independent risk factor was Charlson Comorbidity Index (CCI) for overall complication. CONCLUSIONS: ERCP can be performed safely and successfully in patients aged ≥90 years. Geriatr Gerontol Int 2022; 22: 50-55.


Assuntos
Colangite , Pancreatite , Idoso , Idoso de 80 Anos ou mais , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Humanos , Pancreatite/epidemiologia , Estudos Retrospectivos
5.
Hum Mol Genet ; 31(10): 1610-1621, 2022 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-34849858

RESUMO

Although previous studies identified numerous single nucleotide polymorphisms (SNPs) and their target genes predisposed to prostate cancer (PrCa) risks, SNP-related splicing associations are rarely reported. In this study, we applied distance-based sQTL analysis (sQTLseekeR) using RNA-seq and SNP genotype data from benign prostate tissue (n = 467) and identified significant associations in 3344 SNP-transcript pairs (P ≤ 0.05) at PrCa risk loci. We characterized a common SNP (rs7247241) and its target gene (PPP1R14A) located in chr19q13, an sQTL with risk allele T associated with upregulation of long isoform (P = 9.99E-7). We confirmed the associations in both TCGA (P = 2.42E-24) and GTEX prostate cohorts (P = 9.08E-78). To functionally characterize this SNP, we performed chromatin immunoprecipitation qPCR and confirmed stronger CTCF and PLAGL2 binding in rs7247241 C than T allele. We found that CTCF binding enrichment was negatively associated with methylation level at the SNP site in human cell lines (r = -0.58). Bisulfite sequencing showed consistent association of rs7247241-T allele with nearby sequence CpG hypermethylation in prostate cell lines and tissues. Moreover, the methylation level at CpG sites nearest to the CTCF binding and first exon splice-in (ψ) of PPP1R14A was significantly associated with aggressive phenotype in the TCGA PrCa cohort. Meanwhile, the long isoform of the gene also promoted cell proliferation. Taken together, with the most updated gene annotations, we reported a set of sQTL associated with multiple traits related to human prostate diseases and revealed a unique role of PrCa risk SNP rs7247241 on PPP1R14A isoform transition.


Assuntos
Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata , Alelos , Ilhas de CpG/genética , Metilação de DNA/genética , Proteínas de Ligação a DNA/genética , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Proteínas Musculares , Polimorfismo de Nucleotídeo Único/genética , Neoplasias da Próstata/genética , Isoformas de Proteínas/genética , Proteínas de Ligação a RNA/genética , Fatores de Transcrição/genética
7.
Theor Appl Genet ; 135(2): 591-604, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34762177

RESUMO

KEY MESSAGE: Genome-wide association study, bulked segregant analysis, and genetic analysis delimited the LG locus controlling light-green immature pepper fruits into a 35.07 kbp region on chromosome 10. A strong candidate gene, CaPP2C35, was identified in this region. In pepper (Capsicum annuum L.), the common colors of immature fruits are yellowish white, milky yellow, green, purple, and purplish black. Genes related to dark green, white, and purple immature fruits have been cloned; however, only a few studies have investigated light-green immature fruits. Here, we performed a genetic study using light-green (17C827) and green (17C658) immature fruits. The light-green color of immature fruits was controlled by a single locus-dominant genetic trait compared with the green color of immature fruits. We also performed a genome-wide association study and bulked segregant analysis of immature-fruit color and mapped the LG locus to a 35.07 kbp region on chromosome 10. Only one gene, Capana10g001710, was found in this region. A G-A substitution occurred at the 313th base of the Capana10g001710 coding sequence in 17C827, resulting in the conversion of the α-helix of its encoded PP2C35 protein into a ß-fold. The expression of Capana10g001710 (termed CaPP2C35) in 17C827 was significantly higher than in 17C658. Silencing CaPP2C35 in 17C827 resulted in an increase in chlorophyll content in the exocarp and the appearance of green stripes on the surface of the fruit. These results indicate that CaPP2C35 may be involved in the formation of light-green immature fruits by regulating the accumulation of chlorophyll content in the exocarp. Thus, these findings lay the foundation for further studies and genetic improvement of immature-fruit color in pepper.


Assuntos
Capsicum , Capsicum/fisiologia , Clorofila/metabolismo , Frutas/fisiologia , Estudo de Associação Genômica Ampla , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
8.
Int J Cancer ; 150(1): 80-90, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34520569

RESUMO

A large proportion of heritability for prostate cancer risk remains unknown. Transcriptome-wide association study combined with validation comparing overall levels will help to identify candidate genes potentially playing a role in prostate cancer development. Using data from the Genotype-Tissue Expression Project, we built genetic models to predict normal prostate tissue gene expression using the statistical framework PrediXcan, a modified version of the unified test for molecular signatures and Joint-Tissue Imputation. We applied these prediction models to the genetic data of 79 194 prostate cancer cases and 61 112 controls to investigate the associations of genetically determined gene expression with prostate cancer risk. Focusing on associated genes, we compared their expression in prostate tumor vs normal prostate tissue, compared methylation of CpG sites located at these loci in prostate tumor vs normal tissue, and assessed the correlations between the differentiated genes' expression and the methylation of corresponding CpG sites, by analyzing The Cancer Genome Atlas (TCGA) data. We identified 573 genes showing an association with prostate cancer risk at a false discovery rate (FDR) ≤ 0.05, including 451 novel genes and 122 previously reported genes. Of the 573 genes, 152 showed differential expression in prostate tumor vs normal tissue samples. At loci of 57 genes, 151 CpG sites showed differential methylation in prostate tumor vs normal tissue samples. Of these, 20 CpG sites were correlated with expression of 11 corresponding genes. In this TWAS, we identified novel candidate susceptibility genes for prostate cancer risk, providing new insights into prostate cancer genetics and biology.


Assuntos
Biomarcadores Tumorais/genética , Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata/patologia , Transcriptoma , Estudos de Casos e Controles , Metilação de DNA , Seguimentos , Estudo de Associação Genômica Ampla , Humanos , Masculino , Prognóstico , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/genética , Locos de Características Quantitativas , Estados Unidos/epidemiologia
9.
Genome Med ; 13(1): 141, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34470669

RESUMO

BACKGROUND: Genome-wide association studies (GWAS) have identified over 56 susceptibility loci associated with Alzheimer's disease (AD), but the genes responsible for these associations remain largely unknown. METHODS: We performed a large transcriptome-wide association study (TWAS) leveraging modified UTMOST (Unified Test for MOlecular SignaTures) prediction models of ten brain tissues that are potentially related to AD to discover novel AD genetic loci and putative target genes in 71,880 (proxy) cases and 383,378 (proxy) controls of European ancestry. RESULTS: We identified 53 genes with predicted expression associations with AD risk at Bonferroni correction threshold (P value < 3.38 × 10-6). Based on fine-mapping analyses, 21 genes at nine loci showed strong support for being causal. CONCLUSIONS: Our study provides new insights into the etiology and underlying genetic architecture of AD.


Assuntos
Alelos , Doença de Alzheimer/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Transcriptoma , Doença de Alzheimer/metabolismo , Mapeamento Cromossômico , Biologia Computacional/métodos , Bases de Dados Genéticas , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Modelos Biológicos , Especificidade de Órgãos/genética , Polimorfismo de Nucleotídeo Único , Prognóstico , Resorcinóis , Transdução de Sinais
10.
Cancer Epidemiol Biomarkers Prev ; 30(11): 2079-2087, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34497089

RESUMO

BACKGROUND: The role of methylation in pancreatic cancer risk remains unclear. We integrated genome and methylome data to identify CpG sites (CpG) with the genetically predicted methylation to be associated with pancreatic cancer risk. We also studied gene expression to understand the identified associations. METHODS: Using genetic data and white blood cell methylation data from 1,595 subjects of European descent, we built genetic models to predict DNA methylation levels. After internal and external validation, we applied prediction models with satisfactory performance to the genetic data of 8,280 pancreatic cancer cases and 6,728 controls of European ancestry to investigate the associations of predicted methylation with pancreatic cancer risk. For associated CpGs, we compared their measured levels in pancreatic tumor versus benign tissue. RESULTS: We identified 45 CpGs at nine loci showing an association with pancreatic cancer risk, including 15 CpGs showing an association independent from identified risk variants. We observed significant correlations between predicted methylation of 16 of the 45 CpGs and predicted expression of eight adjacent genes, of which six genes showed associations with pancreatic cancer risk. Of the 45 CpGs, we were able to compare measured methylation of 16 in pancreatic tumor versus benign pancreatic tissue. Of them, six showed differentiated methylation. CONCLUSIONS: We identified methylation biomarker candidates associated with pancreatic cancer using genetic instruments and added additional insights into the role of methylation in regulating gene expression in pancreatic cancer development. IMPACT: A comprehensive study using genetic instruments identifies 45 CpG sites at nine genomic loci for pancreatic cancer risk.


Assuntos
Metilação de DNA , Neoplasias Pancreáticas , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Ilhas de CpG/genética , Epigenoma , Humanos , Neoplasias Pancreáticas/genética
11.
Cancer Commun (Lond) ; 41(12): 1387-1397, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34520132

RESUMO

BACKGROUND: DNA methylation and gene expression are known to play important roles in the etiology of human diseases such as prostate cancer (PCa). However, it has not yet been possible to incorporate information of DNA methylation and gene expression into polygenic risk scores (PRSs). Here, we aimed to develop and validate an improved PRS for PCa risk by incorporating genetically predicted gene expression and DNA methylation, and other genomic information using an integrative method. METHODS: Using data from the PRACTICAL consortium, we derived multiple sets of genetic scores, including those based on available single-nucleotide polymorphisms through widely used methods of pruning and thresholding, LDpred, LDpred-funt, AnnoPred, and EBPRS, as well as PRS constructed using the genetically predicted gene expression and DNA methylation through a revised pruning and thresholding strategy. In the tuning step, using the UK Biobank data (1458 prevalent cases and 1467 controls), we selected PRSs with the best performance. Using an independent set of data from the UK Biobank, we developed an integrative PRS combining information from individual scores. Furthermore, in the testing step, we tested the performance of the integrative PRS in another independent set of UK Biobank data of incident cases and controls. RESULTS: Our constructed PRS had improved performance (C statistics: 76.1%) over PRSs constructed by individual benchmark methods (from 69.6% to 74.7%). Furthermore, our new PRS had much higher risk assessment power than family history. The overall net reclassification improvement was 69.0% by adding PRS to the baseline model compared with 12.5% by adding family history. CONCLUSIONS: We developed and validated a new PRS which may improve the utility in predicting the risk of developing PCa. Our innovative method can also be applied to other human diseases to improve risk prediction across multiple outcomes.


Assuntos
Metilação de DNA , Neoplasias da Próstata , Metilação de DNA/genética , Expressão Gênica , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Masculino , Herança Multifatorial , Neoplasias da Próstata/genética , Fatores de Risco
12.
Pharmgenomics Pers Med ; 14: 1211-1220, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34588798

RESUMO

BACKGROUND: Previous studies suggest a potential link between glycosylation and prostate cancer. To better characterize the relationship between the two, we performed a study to comprehensively evaluate the associations between genetically predicted blood plasma N-glycan levels and prostate cancer risk. METHODS: Using genetic variants associated with N-glycan levels as instruments, we evaluated the associations between levels of 138 plasma N-glycans and prostate cancer risk. We analyzed data of 79,194 cases and 61,112 controls of European ancestry included in the consortia of BPC3, CAPS, CRUK, PEGASUS, and PRACTICAL. RESULTS: We identified three N-glycans with genetically predicted levels in plasma to be associated with prostate cancer risk after Bonferroni correction. The estimated odds ratios (95% confidence intervals) were 1.29 (1.20-1.40), 0.80 (0.74-0.88), and 0.79 (0.72-0.87) for PGP18, PGP33, and PGP109, respectively, per every one standard deviation increase in genetically predicted levels of N-glycan. However, the instruments for these N-glycans only involved one to two variants. The proportions of variations that can be explained by the instruments range from 1.58% to 2.95% for these three N-glycans. CONCLUSION: We observed associations between genetically predicted levels of three N-glycans PGP18, PGP33, and PGP109 and prostate cancer risk. Given the correlated nature of the N-glycans and that many N-glycans share genetic loci, pleiotropy is a major concern. Future work is warranted to better characterize the relationship between N-glycans and prostate cancer.

13.
Hum Mol Genet ; 31(2): 289-299, 2021 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-34387340

RESUMO

Alzheimer's disease (ad) adversely affects the health, quality of life and independence of patients. There is a critical need to identify novel blood gene biomarkers for ad risk assessment. We performed a transcriptome-wide association study to identify biomarker candidates for ad risk. We leveraged two sets of gene expression prediction models of blood developed using different reference panels and modeling strategies. By applying the prediction models to a meta-GWAS including 71 880 (proxy) cases and 383 378 (proxy) controls, we identified significant associations of genetically determined expression of 108 genes in blood with ad risk. Of these, 15 genes were differentially expressed between ad patients and controls with concordant directions in measured expression data. With evidence from the analyses based on both genetic instruments and directly measured expression levels, this study identifies 15 genes with strong support as biomarkers in blood for ad risk, which may enhance ad risk assessment and mechanism-focused studies.


Assuntos
Doença de Alzheimer , Doença de Alzheimer/genética , Marcadores Genéticos , Estudo de Associação Genômica Ampla , Humanos , Polimorfismo de Nucleotídeo Único/genética , Qualidade de Vida , Transcriptoma/genética
14.
Brain Stimul ; 14(5): 1147-1153, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34365019

RESUMO

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is an efficacious and well-tolerated intervention for treatment-resistant depression (TRD). A novel rTMS protocol, intermittent theta burst stimulation (iTBS) has been recently implemented in clinical practice, and it is essential to characterize the factors associated to pain and the trajectory of pain of iTBS compared to standard rTMS protocols. OBJECTIVE: We aimed to characterize the side effect profile and the pain trajectories of High-Frequency Left (HFL) and iTBS in TRD patients in the THREE-D trial. We also investigated factors associated to pain and the relationship between pain and clinical outcomes. METHODS: 414 patients were randomized to either HFL or iTBS. Severity of pain was measured after every treatment. General Estimating Equation was used to investigate factors associated with pain. Latent class linear mixed model was used to investigate latent classes of pain trajectories over the course of rTMS. RESULTS: Higher level of pain was associated with older age, higher stimulation intensity, higher anxiety, female, and non-response. The severity of pain significantly declined over the course of treatments with a steeper decrease early on in the course of the treatment in both protocols, and four latent pain trajectories were identified. The less favorable pain trajectories were associated with non-response and higher stimulation intensity. CONCLUSIONS: HFL and iTBS were associated with similar factors and pain trajectories, although iTBS was more uncomfortable. Response to rTMS was associated with less pain and more favorable pain trajectories furthering the evince base of overlapping neurobiological underpinnings of mood and pain. We translated these results into patient-oriented information to aid in the decision-making process when considering rTMS.


Assuntos
Transtorno Depressivo Maior , Estimulação Magnética Transcraniana , Idoso , Feminino , Humanos , Dor , Córtex Pré-Frontal , Resultado do Tratamento
15.
Genet Epidemiol ; 45(8): 848-859, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34255882

RESUMO

Transcriptome-wide association studies (TWAS) that integrate transcriptomic reference data and genome-wide association studies (GWAS) have successfully enhanced the discovery of candidate genes for many complex traits. However, existing methods may suffer from substantial power loss because they fail to effectively consider that expression of many genes tends to be consistent across tissues. Here we propose a computationally efficient testing method, referred to as Integrative Test for Associations via Cauchy Transformation (InTACT), that effectively combines information across multiple tissues and thus improves the power of identifying associated genes. Through simulation studies, we show that InTACT maintains high power while properly controls for Type 1 error rates. We applied InTACT to the largest GWAS of Alzheimer's disease (AD) to date and identified 227 genome-wide significant genes, of which 130 were not identified by benchmark methods, TWAS and MultiXcan. Importantly, InTACT identified five novel loci for AD. We implemented InTACT in publicly available software, "InTACT."


Assuntos
Estudo de Associação Genômica Ampla , Transcriptoma , Estudo de Associação Genômica Ampla/métodos , Humanos , Modelos Genéticos , Herança Multifatorial , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas
16.
Genet Med ; 23(11): 2076-2086, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34183789

RESUMO

PURPOSE: It is critical to identify putative causal targets for SARS coronavirus 2, which may guide drug repurposing options to reduce the public health burden of COVID-19. METHODS: We applied complementary methods and multiphased design to pinpoint the most likely causal genes for COVID-19 severity. First, we applied cross-methylome omnibus (CMO) test and leveraged data from the COVID-19 Host Genetics Initiative (HGI) comparing 9,986 hospitalized COVID-19 patients and 1,877,672 population controls. Second, we evaluated associations using the complementary S-PrediXcan method and leveraging blood and lung tissue gene expression prediction models. Third, we assessed associations of the identified genes with another COVID-19 phenotype, comparing very severe respiratory confirmed COVID versus population controls. Finally, we applied a fine-mapping method, fine-mapping of gene sets (FOGS), to prioritize putative causal genes. RESULTS: Through analyses of the COVID-19 HGI using complementary CMO and S-PrediXcan methods along with fine-mapping, XCR1, CCR2, SACM1L, OAS3, NSF, WNT3, NAPSA, and IFNAR2 are identified as putative causal genes for COVID-19 severity. CONCLUSION: We identified eight genes at five genomic loci as putative causal genes for COVID-19 severity.


Assuntos
COVID-19 , Expressão Gênica , Estudo de Associação Genômica Ampla , Humanos , Fenótipo , SARS-CoV-2
17.
Sensors (Basel) ; 21(9)2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-34066938

RESUMO

Three-dimensional feature description for a local surface is a core technology in 3D computer vision. Existing descriptors perform poorly in terms of distinctiveness and robustness owing to noise, mesh decimation, clutter, and occlusion in real scenes. In this paper, we propose a 3D local surface descriptor using point-pair transformation feature histograms (PPTFHs) to address these challenges. The generation process of the PPTFH descriptor consists of three steps. First, a simple but efficient strategy is introduced to partition the point-pair sets on the local surface into four subsets. Then, three feature histograms corresponding to each point-pair subset are generated by the point-pair transformation features, which are computed using the proposed Darboux frame. Finally, all the feature histograms of the four subsets are concatenated into a vector to generate the overall PPTFH descriptor. The performance of the PPTFH descriptor is evaluated on several popular benchmark datasets, and the results demonstrate that the PPTFH descriptor achieves superior performance in terms of descriptiveness and robustness compared with state-of-the-art algorithms. The benefits of the PPTFH descriptor for 3D surface matching are demonstrated by the results obtained from five benchmark datasets.

18.
Int J Cancer ; 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33844845

RESUMO

There is limited evidence on the association between red meat consumption and pancreatic cancer among ethnic minorities. We assessed this relationship in two large prospective cohorts: the Multiethnic Cohort Study (MEC) and the Southern Community Cohort Study (SCCS). Demographic, dietary and other risk factor data were collected at cohort entry. Red meat intake was assessed using cohort-specific validated food frequency questionnaires. Incident pancreatic cancer cases were identified via linkages to state cancer registries. Cox regression was used to calculate relative risks (RRs) and 95% confidence intervals (CIs) for the association of red meat intake with pancreatic cancer risk in each cohort. We performed additional analyses to evaluate cooking methods, mutagens and effect modification by NAT1/2 genotypes. From a total of 184 542 (MEC) and 66 793 (SCCS) at-risk participants, we identified 1618 (MEC) and 266 (SCCS) incident pancreatic cancer cases. Red meat consumption was associated with pancreatic cancer risk in the MEC (RRQ4vsQ1 1.18, 95% CI 1.02-1.37) and with borderline statistical significance in the SCCS (RRQ4vsQ1 1.31, 95% CI 0.93-1.86). This association was significant in African Americans (RRQ4vsQ1 1.49, 95% CI 1.06-2.11) and Latinos (RRQ4vsQ1 1.44, 95% CI 1.02-2.04) in the MEC, and among African Americans (RRQ4vsQ1 1.55, 95% CI 1.03-2.33) in the SCCS. NAT2 genotypes appeared to modify the relationship between red meat and pancreatic cancer in the MEC (pinteraction = 0.03). Our findings suggest that the associations for red meat may be strongest in African Americans and Latinos. The mechanisms underlying the increased risk for these populations should be further investigated.

19.
Stat Med ; 40(13): 3138-3152, 2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-33821528

RESUMO

Nonlinear mixed-effects (NLME) models are commonly used in longitudinal studies such as pharmacokinetics and HIV viral dynamics studies. NLME models are often derived based on underlying data-generating mechanisms, therefore the parameters in these models often have natural physical interpretations that may suggest reasonable constraints on certain parameters. For example, the HIV viral decay rates for populations receiving anti-HIV treatments may be reasonably expected to be nonnegative. Hypothesis testing for these parameters should incorporate practically reasonable constraints to increase statistical power. Motivated from HIV viral dynamic models, in this article we propose multiparameter one-sided or constrained tests for NLME models with censored responses, for example, viral dynamic models with viral loads subject to lower detection limits. We propose approximate likelihood-based tests that are computationally efficient. We evaluate the tests via simulations and show that the proposed tests are more powerful than the corresponding two-sided or unrestricted tests. We apply the proposed tests to two AIDS datasets with new findings.


Assuntos
Modelos Estatísticos , Dinâmica não Linear , Humanos , Funções Verossimilhança , Estudos Longitudinais , Carga Viral
20.
Cancers (Basel) ; 13(9)2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33925895

RESUMO

Endometrial cancer (EC) is the leading female reproductive tract malignancy in developed countries. Currently, genome-wide association studies (GWAS) have identified 17 risk loci for EC. To identify novel EC-associated proteins, we used previously reported protein quantitative trait loci for 1434 plasma proteins as instruments to evaluate associations between genetically predicted circulating protein concentrations and EC risk. We studied 12,906 cases and 108,979 controls of European descent included in the Endometrial Cancer Association Consortium, the Epidemiology of Endometrial Cancer Consortium, and the UK Biobank. We observed associations between genetically predicted concentrations of nine proteins and EC risk at a false discovery rate of <0.05 (p-values range from 1.14 × 10-10 to 3.04 × 10-4). Except for vascular cell adhesion protein 1, all other identified proteins were independent from known EC risk variants identified in EC GWAS. The respective odds ratios (95% confidence intervals) per one standard deviation increase in genetically predicted circulating protein concentrations were 1.21 (1.13, 1.30) for DNA repair protein RAD51 homolog 4, 1.27 (1.14, 1.42) for desmoglein-2, 1.14 (1.07, 1.22) for MHC class I polypeptide-related sequence B, 1.05 (1.02, 1.08) for histo-blood group ABO system transferase, 0.77 (0.68, 0.89) for intestinal-type alkaline phosphatase, 0.82 (0.74, 0.91) for carbohydrate sulfotransferase 15, 1.07 (1.03, 1.11) for D-glucuronyl C5-epimerase, and 1.07 (1.03, 1.10) for CD209 antigen. In conclusion, we identified nine potential EC-associated proteins. If validated by additional studies, our findings may contribute to understanding the pathogenesis of endometrial tumor development and identifying women at high risk of EC along with other EC risk factors and biomarkers.

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