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1.
Phys Med Biol ; 2020 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-33333495

RESUMO

Dynamic myocardial perfusion computed tomography (DMP-CT) is an effective medical imaging technique for coronary artery disease (CAD) diagnosis and therapy guidance. However, the radiation dose received by the patient during repeated CT scans is a widespread concern of radiologists because it increases the risk of cancer. The sparse few-view CT scanning protocol can be a feasible approach to reduce the radiation dose associated with DMP-CT imaging; however, an advanced reconstruction algorithm is needed. In this paper, a temporal feature prior-aided separated reconstruction method (TFP-SR) for low-dose DMP-CT image reconstruction from sparse few-view sinograms is proposed. For the implementation of this method, the objective perfusion image is divided into the baseline fraction and the enhancement fraction introduced by the arrival of the contrast agent. The core of the proposed TFP-SR method is the use of the temporal evolution information that naturally exists in the DMP-CT image sequence to aid the reconstruction of the enhancement image from limited data. The temporal feature vector of an image pixel is defined by the intensities of this pixel in the pre-reconstructed enhancement sequence, and the connection between two related features is calculated via a zero-mean Gaussian function. A prior matrix is constructed based on the connections between the extracted temporal features and used in the iterative reconstruction of the enhancement images. In this paper, the proposed method is evaluated by comparing it to the conventional filtered back-projection (FBP) algorithm, total variation-regularized penalized weighted least squares (PWLS-TV) and prior image constrained compressed sensing (PICCS) based on studies of a digital extended cardiac-torso (XCAT) thoracic phantom and a preclinical porcine DMP-CT data set that takes image misregistration into account. The experimental results demonstrate that the proposed TFP-SR method has superior performance in sparse DMP-CT image reconstruction in terms of the image quality, time-attenuation curve (TAC), and hemodynamic parameters.

2.
JAMA Psychiatry ; 2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33263727

RESUMO

Importance: The genetic basis of bipolar disorder (BD) in Han Chinese individuals is not fully understood. Objective: To explore the genetic basis of BD in the Han Chinese population. Design, Setting, and Participants: A genome-wide association study (GWAS), followed by independent replication, was conducted to identify BD risk loci in Han Chinese individuals. Individuals with BD were diagnosed based on DSM-IV criteria and had no history of schizophrenia, mental retardation, or substance dependence; individuals without any personal or family history of mental illnesses, including BD, were included as control participants. In total, discovery samples from 1822 patients and 4650 control participants passed quality control for the GWAS analysis. Replication analyses of samples from 958 patients and 2050 control participants were conducted. Summary statistics from the European Psychiatric Genomics Consortium 2 (PGC2) BD GWAS (20 352 cases and 31 358 controls) were used for the trans-ancestry genetic correlation analysis, polygenetic risk score analysis, and meta-analysis to compare BD genetic risk between Han Chinese and European individuals. The study was performed in February 2020. Main Outcomes and Measures: Single-nucleotide variations with P < 5.00 × 10-8 were considered to show genome-wide significance of statistical association. Results: The Han Chinese discovery GWAS sample included 1822 cases (mean [SD] age, 35.43 [14.12] years; 838 [46%] male) and 4650 controls (mean [SD] age, 27.48 [5.97] years; 2465 [53%] male), and the replication sample included 958 cases (mean [SD] age, 37.82 [15.54] years; 412 [43%] male) and 2050 controls (mean [SD] age, 27.50 [6.00] years; 1189 [58%] male). A novel BD risk locus in Han Chinese individuals was found near the gene encoding transmembrane protein 108 (TMEM108, rs9863544; P = 2.49 × 10-8; odds ratio [OR], 0.650; 95% CI, 0.559-0.756), which is required for dendritic spine development and glutamatergic transmission in the dentate gyrus. Trans-ancestry genetic correlation estimation (ρge = 0.652, SE = 0.106; P = 7.30 × 10-10) and polygenetic risk score analyses (maximum liability-scaled Nagelkerke pseudo R2 = 1.27%; P = 1.30 × 10-19) showed evidence of shared BD genetic risk between Han Chinese and European populations, and meta-analysis identified 2 new GWAS risk loci near VRK2 (rs41335055; P = 4.98 × 10-9; OR, 0.849; 95% CI, 0.804-0.897) and RHEBL1 (rs7969091; P = 3.12 × 10-8; OR, 0.932; 95% CI, 0.909-0.956). Conclusions and Relevance: This GWAS study identified several loci and genes involved in the heritable risk of BD, providing insights into its genetic architecture and biological basis.

3.
Front Psychiatry ; 11: 559210, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33173509

RESUMO

Objective: Schizophrenia (SZ) is a common and complex psychiatric disorder that has a significant genetic component. The glutamate hypothesis describes one possible pathogenesis of SZ. The solute carrier family 1 gene (SLC1A1) is one of several genes thought to play a critical role in regulating the glutamatergic system and is strongly implicated in the pathophysiology of SZ. In this study, we identify polymorphisms of the SLC1A1 gene that may confer susceptibility to SZ in the Han Chinese population. Methods: We genotyped 36 single-nucleotide polymorphisms (SNPs) using Illumina GoldenGate assays on a BeadStation 500G Genotyping System in 528 paranoid SZ patients and 528 healthy controls. Psychopathology was rated by the Positive and Negative Symptom Scale. Results: Significant associations were found in genotype and allele frequencies for SNPs rs10815017 (p = 0.002, 0.030, respectively) and rs2026828 (p = 0.020, 0.005, respectively) between SZ and healthy controls. There were significant associations in genotype frequency at rs6476875 (p = 0.020) and rs7024664 (p = 0.021) and allele frequency at rs3780412 (p = 0.026) and rs10974573 (p = 0.047) between SZ and healthy controls. Meanwhile, significant differences were found in genotype frequency at rs10815017 (p = 0.015), rs2026828 (p = 0.011), and rs3780411 (p = 0.040) in males, and rs7021569 in females (p = 0.020) between cases and controls when subdivided by gender. Also, significant differences were found in allele frequency at rs2026828 (p = 0.003), and rs7021569 (p = 0.045) in males, and rs10974619 in females (p = 0.044). However, those associations disappeared after Bonferroni's correction (p's > 0.05). Significant associations were found in the frequencies of four haplotypes (AA, CA, AGA, and GG) between SZ and healthy controls (χ 2 = 3.974, 7.433, 4.699, 4.526, p = 0.046, 0.006, 0.030, 0.033, respectively). There were significant associations between rs7032326 genotypes and PANSS total, positive symptoms, negative symptoms, and general psychopathology in SZ (p = 0.002, 0.011, 0.028, 0.008, respectively). Conclusion: The present study provides further evidence that SLC1A1 may be not a susceptibility gene for SZ. However, the genetic variations of SLC1A1 may affect psychopathology symptoms.

4.
Psychiatry Res ; : 113578, 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33243520

RESUMO

Schizophrenia is considered a connectivity disorder. Further, the functional connectivity (FC) of the default-mode network (DMN) has gained the interest of researchers. However, few studies have been conducted on the abnormal connectivity of DMN in early-onset schizophrenia (EOS). In this study, the key brain regions of the DMN were used as seed regions to analyze the FC of the whole brain in EOS. When the seed was located in the medial prefrontal cortex (mPFC), patients with EOS exhibited decreased FC between mPFC and other brain regions compared with healthy controls (voxel P value < 0.001, cluster P value < 0.05, Gaussian random field corrected). When the seed was located in the posterior cingulate cortex (PCC), the FC between PCC and other brain regions was enhanced and weakened (voxel P value < 0.001, cluster P value < 0.05, Gaussian random field corrected), and PCC connectivity with the right parahippocampal gyrus was associated with Positive and Negative Syndrome Scale scores for the general score (r = -0.315, P = 0.02). The results showed that the FC within the DMN and that between DMN and visual networks were abnormal, suggesting that the DMN might be involved in the pathogenesis of EOS.

5.
JGH Open ; 4(5): 1009-1011, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33102778

RESUMO

Crigler-Najjar syndrome (CNs) is a rare hereditary unconjugated hyperbilirubinemia caused by mutations in the bilirubin Uridine (UDP) glucuronosyltransferase family 1 member A1 (UGT1A1, ENSG00000241635) gene. Two patients were clinically diagnosed with Crigler-Najjar Syndrome types II (CNs-II) can be clinically diagnosed which were based on the level of total bilirubin, efficacy of phenobarbital treatment, normal liver architecture and exclusion of hemolysis. Diagnosis was also confirmed by UGT1A1 gene mutations, which by sequencing the coding region for UGT1A1 gene mutations, which were the homozygous mutations c.668G > A/p.Cys223Tyr and which caused less than 10% of activity of the enzyme. No data have been reported about this mutate in the population. These patients have a good prognosis and require no active intervention, indicating that an early accurate diagnosis is necessary for disease management and genetic counseling.

6.
Front Oncol ; 10: 1408, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33014779

RESUMO

Objectives: Acute kidney injury (AKI) is a recently observed side effect in patients after microwave ablation (MWA) of hepatocellular carcinoma (HCC) and is associated with negative outcomes. The aim of this study is to explore the risk factors of affecting the occurrence of AKI (stages 1b, 2, and 3), because they have a higher mortality rate than patients with AKI (stage 1a) and without AKI. Materials and methods: In this retrospective study, a total of 1,214 patients with HCC who were treated with MWA under ultrasound (US) guidance in our department between January 2005 and November 2017 were enrolled. We evaluated the influence of 20 risk factors. Univariate and multivariate analysis were used for statistical analysis. The possible risk factors of AKI after MWA for HCC were summarized. Results: AKI, AKI (stage 1a), and AKI (stages 1b, 2, and 3) after MWA were found in 34, 15, and 19 patients (2.80, 1.24, and 1.57%), respectively. Among 34 patients with AKI, 10 cases with AKI (stage 1a) and 6 cases with AKI (stages 1b, 2, and 3) recovered before their discharge without any treatment for AKI and 9 cases with AKI (stages 1b, 2, and 3) with further treatment. Four cases who had chronic renal failure before MWA of liver accepted renal dialysis. By univariate analysis, the number of antenna insertions (P = 0.027, OR = 3.3), MWA time ≥20 min (P = 0.029, OR = 4.3), creatinine (Cr)-pre above the upper limit of the reference value (P < 0.001, OR = 35.5), albumin (Alb)-pre (P = 0.030, OR = 0.9), and red blood cell (RBC)-pre (P < 0.001, OR = 0.3) were significant risk factors. By multivariate analysis, Cr-pre ≥ 110 µmol/L (P < 0.001, OR = 31.4) and MWA time ≥20 min (P = 0.043 OR = 9.9) were the independent risk factors. Conclusion: AKI (stages 1b, 2, and 3) is a relatively serious complication after MWA for HCC, which is related to MWA time and Cr-pre. It requires attention by clinicians. So it is of great necessity to assess the Cr-pre level and reduce the MWA time to <20 min to minimize the risk of AKI after MWA for HCC.

7.
Liver Int ; 40(11): 2685-2693, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33047868

RESUMO

BACKGROUND & AIM: An affordable, pangenotypic regimen remains as an unmet medical need for chronic hepatitis C patients in China. This single-arm, open-label, multicenter, phase 3 trial evaluated the efficacy and safety of coblopasvir, a pangenotypic non-structural protein 5A (NS5A) inhibitor, combined with sofosbuvir for treating Chinese patients with chronic hepatitis C virus (HCV) infection. METHODS: Treatment-naïve and interferon-experienced adult patients, including those with advanced fibrosis (F3) or compensated cirrhosis (F4), were treated with a universal, combinational regimen of coblopasvir 60 mg and sofosbuvir 400 mg, once daily, for 12 weeks. The primary efficacy endpoint was sustained virological response at post-treatment week 12 (SVR12). RESULTS: Overall, 371 patients (men, 51%; age, 47 ± 11 years; genotype 1a < 1%, 1b 48%, 2a 26%, 3a 6%, 3b 7% and 6 12%) were enrolled from 19 sites. Fifty-one patients (14%) had F3, 39 patients (11%) had F4 and 39 patients (11%) were interferon experienced. The overall SVR12 was 97% (95% CI, [94%, 98%]) for the full analysis set and was equal to or above 90% for all predefined subsets. Ten patients (3%) experienced virological relapse and two patients did not complete follow-up. No adverse events (AEs) occurred at a frequency ≥5%, and the most often reported AEs (≥1%) were neutropenia and fatigue. The majority of AEs were mild to moderate and transient without specific medical intervention. CONCLUSIONS: The universal, pangenotypic combo of coblopasvir plus sofosbuvir is an efficacious and safe treatment for Chinese patients monoinfected with HCV of genotype 1, 2, 3 and 6, including those with compensated cirrhosis. LAY SUMMARY: The regimen of coblopasvir and sofosbuvir is a safe and effective treatment for Chinese patients with genotype 1, 2, 3 and 6 HCV infection, including those with compensated cirrhosis. Therefore, this regimen would be a novel choice of treatment for this patient population.

8.
Phys Med Biol ; 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33120378

RESUMO

Many deep learning (DL)-based image restoration methods for low-dose CT problems directly employ the end-to-end networks on low-dose training data without considering dose differences. However, the radiation dose difference has a great impact on the ultimate results, and lower doses increase the difficulty of restoration. Moreover, there is increasing demand to design and estimate acceptable scanning doses for patients in clinical practice, necessitating dose-aware networks embedded with adaptive dose estimation. In this paper, we consider these dose differences of input low-dose CT images and propose an adaptive dose-aware network. First, considering a large dose distribution range for simulation convenience, we coarsely define 5 dose levels in advance as lowest, lower, mild, higher and highest radiation dose levels. Instead of directly building the end-to-end mapping function between low-dose CT (LDCT) images and high-dose CT (HDCT) counterparts, the dose level is primarily estimated in the first stage. In the second stage, the adaptively learned low-dose level is used to guide the image restoration process as the pattern of prior information through the channel feature transform (CFT). We conduct experiments on a simulated dataset based on original high dose parts of AAPM challenge datasets from the Mayo Clinic. Ablation studies validate the effectiveness of the dose-level estimation, and the experimental results show that our method is superior to several other DL-based methods. Specifically, our method provides obviously better performance in terms of the peak signal-to-noise ratio (PSNR) and visual quality reflected in subjective scores. Due to the dual-stage process, our method may suffer limitations under more parameters and coarse dose-level definitions, and thus, further improvements in clinical practical applications with different CT equipment vendors are planned in future work.

9.
J Clin Transl Hepatol ; 8(3): 255-261, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-33083247

RESUMO

Background and Aims: Emitasvir is a new type of hepatitis C virus (HCV) nonstructural protein 5A (NS5A) inhibitor, and the data of phase 2 trial has shown emitasvir-sofosbuvir to have good safety and tolerance. We conducted this phase 3 trial to further verify the efficacy and safety. Methods: We evaluated the antiviral activity and safety of a 12-week regimen of emitasvir phosphate (100 mg) combined with sofosbuvir (400 mg) once daily in non-cirrhotic patients with genotype 1 HCV infection. The primary endpoint was a sustained virological response at 12 weeks (SVR12) after the end of treatment. Results: Of the 362 patients enrolled in the trial, 39.8% were male, 99.2% had HCV genotype 1b, 0.8% had genotype 1a and 79.8% were treatment-naïve. The average age was 47.2 years. All patients completed the treatment and follow-up. All 3 patients with genotype 1a achieved SVR. Two genotype 1b treatment-naïve patients experienced virologic relapse. The rate of SVR12 was 99.7% (358/359), and SVR24 was 99.4% (357/359) in genotype 1b. Overall, 36.2% had resistance-associated substitutions (RASs) in NS5A and 98.3% had RASs in NS5B at baseline. The RASs at baseline had no effect on the rates of response. Serious adverse events were reported in 16 patients and were not related to emitasvir-sofosbuvir. Most adverse events did not require therapy. Conclusions: The 12 weeks of treatment with emitasvir-sofosbuvir was a highly efficient and safe treatment for a wide range of patients with HCV genotype 1b infection without cirrhosis, who had not been treated or who had been treated with interferon-based regimen previously.

10.
J Xray Sci Technol ; 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33044223

RESUMO

BACKGROUND: Radiation risk from computed tomography (CT) is always an issue for patients, especially those in clinical conditions in which repeated CT scanning is required. For patients undergoing repeated CT scanning, a low-dose protocol, such as sparse scanning, is often used, and consequently, an advanced reconstruction algorithm is also needed. OBJECTIVE: To develop a novel algorithm used for sparse-view CT reconstruction associated with the prior image. METHODS: A low-dose CT reconstruction method based on prior information of normal-dose image (PI-NDI) involving a transformed model for attenuation coefficients of the object to be reconstructed and prior information application in the forward-projection process was used to reconstruct CT images from sparse-view projection data. A digital extended cardiac-torso (XCAT) ventral phantom and a diagnostic head phantom were employed to evaluate the performance of the proposed PI-NDI method. The root-mean-square error (RMSE), peak signal-to-noise ratio (PSNR) and mean percent absolute error (MPAE) of the reconstructed images were measured for quantitative evaluation of the proposed PI-NDI method. RESULTS: The reconstructed images with sparse-view projection data via the proposed PI-NDI method have higher quality by visual inspection than that via the compared methods. In terms of quantitative evaluations, the RMSE measured on the images reconstructed by the PI-NDI method with sparse projection data is comparable to that by MLEM-TV, PWLS-TV and PWLS-PICCS with fully sampled projection data. When the projection data are very sparse, images reconstructed by the PI-NDI method have higher PSNR values and lower MPAE values than those from the compared algorithms. CONCLUSIONS: This study presents a new low-dose CT reconstruction method based on prior information of normal-dose image (PI-NDI) for sparse-view CT image reconstruction. The experimental results validate that the new method has superior performance over other state-of-art methods.

11.
Phys Med Biol ; 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32992302

RESUMO

In this work, a small animal PET scanner named SIAT aPET was developed using dual-ended readout depth encoding detectors to simultaneously achieve high spatial resolution and high sensitivity. The scanner consists of 4 detector rings with 12 detector modules per ring; the ring diameter is 111 mm and the axial field of view is 105.6 mm. The images are reconstructed using an ordered subset expectation maximization (OSEM) algorithm. The spatial resolution of the scanner was measured by using a 22Na point source at the center axial field of view with different radial offsets. The sensitivity of the scanner was measured at center axis of the scanner with different axial positions. The count rate performance of the system was evaluated by scanning mouse-sized and rat-sized phantoms. An ultra-micro hot-rods phantom and two mice injected with 18F-NaF and 18F-FDG were scanned on the scanner. An average DOI resolution of 1.96 mm, energy resolution of 19.1% and timing resolution of 1.20 ns were obtained for the detector. Average spatial resolutions of 0.82 mm and 1.16 mm were obtained up to a distance of 30 mm radially from the center of the field of view when reconstructing a point source in 1% and 10% warm backgrounds, respectively, using OSEM reconstruction with 16 subsets and 10 iterations. Sensitivities of 16.0% and 11.9% were achieved at center of the scanner for energy windows of 250-750 keV and 350-750 keV respectively. Peak noise equivalent count rates of 324 kcps and 144 kcps were obtained at an activity of 26.4 MBq for the mouse-sized and rat-sized phantoms. Rods of 1.0 mm diameter can be visually resolved from the image of the ultra-micro hot-rods phantom. The capability of the scanner was demonstrated by high quality in-vivo mouse images.

12.
Zool Res ; 41(6): 632-643, 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-32987454

RESUMO

Accumulating studies have been conducted to identify risk genes and relevant biological mechanisms underlying major depressive disorder (MDD). In particular, transcriptomic analyses in brain regions engaged in cognitive and emotional processes, e.g., the dorsolateral prefrontal cortex (DLPFC), have provided essential insights. Based on three independent DLPFC RNA-seq datasets of 79 MDD patients and 75 healthy controls, we performed differential expression analyses using two alternative approaches for cross-validation. We also conducted transcriptomic analyses in mice undergoing chronic variable stress (CVS) and chronic social defeat stress (CSDS). We identified 12 differentially expressed genes (DEGs) through both analytical methods in MDD patients, the majority of which were also dysregulated in stressed mice. Notably, the mRNA level of the immediate early gene FOS ( Fos proto-oncogene) was significantly decreased in both MDD patients and CVS-exposed mice, and CSDS-susceptible mice exhibited a greater reduction in Fos expression compared to resilient mice. These findings suggest the potential key roles of this gene in the pathogenesis of MDD related to stress exposure. Altered transcriptomes in the DLPFC of MDD patients might be, at least partially, the result of stress exposure, supporting that stress is a primary risk factor for MDD.

13.
J Med Genet ; 2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32900838

RESUMO

The association between NOTCH4 and schizophrenia has been repeatedly reported. However, the results from different genetic studies are inconsistent, and the role of NOTCH4 in schizophrenia pathogenesis remains unknown. Here, we provide convergent lines of evidence that support NOTCH4 as a schizophrenia risk gene. We first performed a meta-analysis and found that a genetic variant (rs2071287) in NOTCH4 was significantly associated with schizophrenia (a total of 125 848 subjects, p=8.31×10-17), with the same risk allele across all tested samples. Expression quantitative trait loci (eQTL) analysis showed that rs2071287 was significantly associated with NOTCH4 expression (p=1.08×10-14) in human brain tissues, suggesting that rs2071287 may confer schizophrenia risk through regulating NOTCH4 expression. Sherlock integrative analysis using a large-scale schizophrenia GWAS and eQTL data from human brain tissues further revealed that NOTCH4 was significantly associated with schizophrenia (p=4.03×10-7 in CMC dataset and p=3.06×10-6 in xQTL dataset), implying that genetic variants confer schizophrenia risk through modulating NOTCH4 expression. Consistently, we found that NOTCH4 was significantly downregulated in brains of schizophrenia patients compared with controls (p=2.53×10-3), further suggesting that dysregulation of NOTCH4 may have a role in schizophrenia. Finally, we showed that NOTCH4 regulates proliferation, self-renewal, differentiation and migration of neural stem cells, suggesting that NOTCH4 may confer schizophrenia risk through affecting neurodevelopment. Our study provides convergent lines of evidence that support the involvement of NOTCH4 in schizophrenia. In addition, our study also elucidates a possible mechanism for the role of NOTCH4 in schizophrenia pathogenesis.

14.
J Xray Sci Technol ; 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32925159

RESUMO

Breast cancer is the most frequently diagnosed cancer in women worldwide. Digital breast tomosynthesis (DBT), which is based on limited-angle tomography, was developed to solve tissue overlapping problems associated with traditional breast mammography. However, due to the problems associated with tube movement during the process of data acquisition, stationary DBT (s-DBT) was developed to allow the X-ray source array to stay stationary during the DBT scanning process. In this work, we evaluate four widely used and investigated DBT image reconstruction algorithms, including the commercial Feldkamp-Davis-Kress algorithm (FBP), the simultaneous iterative reconstruction technique (SIRT), the simultaneous algebraic reconstruction technique (SART) and the total variation regularized SART (SART-TV) for an s-DBT imaging system that we set up in our own laboratory for studies using a semi-elliptical digital phantom and a rubber breast phantom to determine the most superior algorithm for s-DBT image reconstruction among the four algorithms. Several quantitative indexes for image quality assessment, including the peak signal-noise ratio (PSNR), the root mean square error (RMSE) and the structural similarity (SSIM), are used to determine the best algorithm for the imaging system that we set up. Image resolutions are measured via the calculation of the contrast-to-noise ratio (CNR) and artefact spread function (ASF). The experimental results show that the SART-TV algorithm gives reconstructed images with the highest PSNR and SSIM values and the lowest RMSE values in terms of image accuracy and similarity, along with the highest CNR values calculated for the selected features and the best ASF curves in terms of image resolution in the horizontal and vertical directions. Thus, the SART-TV algorithm is proven to be the best algorithm for use in s-DBT image reconstruction for the specific imaging task in our study.

15.
Artigo em Inglês | MEDLINE | ID: mdl-32791513

RESUMO

Genetic analyses for bipolar disorder (BD) have achieved prominent success in Europeans in recent years, whereas its genetic basis in other populations remains relatively less understood. We herein report that the leading risk locus for BD in European genome-wide association studies (GWAS), the single-nucleotide polymorphism (SNP) rs9834970 near TRANK1 at 3p22 region, is also genome-wide significantly associated with BD in a meta-analysis of four independent East Asian samples including 5748 cases and 65,361 controls (p = 2.27 × 10-8, odds ratio = 1.136). Expression quantitative trait loci (eQTL) analyses and summary data-based Mendelian randomization (SMR) analyses in multiple human brain samples suggest that lower TRANK1 mRNA expression is a principal BD risk factor explaining its genetic risk signals at 3p22. We also identified another SNP rs4789 in the 3' untranslated region (3'UTR) of TRANK1 showing stronger eQTL associations as well as genome-wide significant association with BD. Despite the relatively unclear neuronal function of TRANK1, our mRNA expression analyses in the human brains and in rat primary cortical neurons reveal that genes highly correlated with TRANK1 are significantly enriched in the biological processes related to dendritic spine, synaptic plasticity, axon guidance and circadian entrainment, and are also more likely to exhibit strong associations in psychiatric GWAS (e.g., the CACNA1C gene). Overall, our results support that TRANK1 is a potential BD risk gene. Further studies elucidating its roles in this illness are needed.

16.
Medicine (Baltimore) ; 99(34): e21408, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846758

RESUMO

Noninvasive tests for the assessment of liver fibrosis are highly needed for the management of patients with autoimmune hepatitis (AIH). We aimed to investigate the accuracy of red cell distribution width to platelet ratio (RPR) in predicting liver fibrosis in AIH patients. One hundred nineteen AIH patients who underwent liver biopsy were enrolled. Liver fibrosis stage was diagnosed using the Scheuer scoring system. The diagnostic accuracy was evaluated by the area under the receiver operating characteristic curve (AUROC). RPR values in AIH patients with S2-S4 (0.10, interquartile range [IQR] 0.08-0.15), S3-S4 (0.10, IQR 0.09-0.14), and S4 (0.14, IQR 0.09-0.19) were significantly higher than patients with S0-S1 (0.07, IQR 0.06-0.08, P < .001), S0-S2 (0.08, IQR 0.06-0.12, P = .025) and S0-S3 (0.09, IQR 0.07-0.13, P = .014), respectively. The RPR was positively correlated with fibrosis stages (r = 0.412, P < .001), while aspartate transaminase to platelet ratio index (APRI) and fibrosis-4 score (FIB-4) were not significantly associated with fibrosis stages in AIH patients. The AUROCs of RPR in identifying significant fibrosis (S2-S4), advanced fibrosis (S3-S4), and cirrhosis (S4) were 0.780 (95% confidence interval [CI] 0.696-0.865), 0.639 (95% CI 0.530-0.748), and 0.724 (95% CI 0.570-0.878), respectively. The AUROCs of RPR were significantly higher than APRI and FIB-4 in diagnosing significant fibrosis, advanced fibrosis, and cirrhosis. Our study demonstrates that the RPR is a simple predictor of liver fibrosis and is superior to APRI and FIB-4 in identifying liver fibrosis in AIH patients.


Assuntos
Hepatite Autoimune/complicações , Cirrose Hepática/sangue , Índices de Eritrócitos , Feminino , Hepatite Autoimune/sangue , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
17.
Phys Med Biol ; 65(21): 215010, 2020 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-32663812

RESUMO

Positron emission tomography (PET) imaging plays an indispensable role in early disease detection and postoperative patient staging diagnosis. However, PET imaging requires not only additional computed tomography (CT) imaging to provide detailed anatomical information but also attenuation correction (AC) maps calculated from CT images for precise PET quantification, which inevitably demands that patients undergo additional doses of ionizing radiation. To reduce the radiation dose and simultaneously obtain high-quality PET/CT images, in this work, we present an alternative based on deep learning that can estimate synthetic attenuation corrected PET (sAC PET) and synthetic CT (sCT) images from non-attenuation corrected PET (NAC PET) scans for whole-body PET/CT imaging. Our model consists of two stages: the first stage removes noise and artefacts in the NAC PET images to generate sAC PET images, and the second stage synthesizes CT images from the sAC PET images obtained in the first stage. Both stages employ the same deep Wasserstein generative adversarial network and identical loss functions, which encourage the proposed model to generate more realistic and satisfying output images. To evaluate the performance of the proposed algorithm, we conducted a comprehensive study on a total of 45 sets of paired PET/CT images of clinical patients. The final experimental results demonstrated that both the generated sAC PET and sCT images showed great similarity to true AC PET and true CT images based on both qualitative and quantitative analyses. These results also indicate that in the future, our proposed algorithm has tremendous potential for reducing the need for additional anatomic imaging in hybrid PET/CT systems or the need for lengthy MR sequence acquisition in hybrid PET/MRI systems.

18.
Phys Med Biol ; 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32679581

RESUMO

In this work a GPU-accelerated fully 3D ordered-subset expectation maximization (OSEM) image reconstruction with point spread function (PSF) modeling was developed for a small animal PET scanner with long axial field of view (FOV). Dual-ended readout detectors that provided high depth of interaction (DOI) resolution were used for the small animal PET scanner to simultaneously achieve uniform high spatial resolution and high sensitivity. First we developed a novel sinogram generation method that the dimension of the sinogram was determined first and then an event was assigned to a few neighboring sinogram elements by using weights that are inversely proportional to the distance from the measured line of response (LOR) to the LOR of the sinogram elements. System geometric symmetry, precomputation of LOR-driven ray-tracing and texture memory were applied to accelerate the GPU based reconstruction. We developed a spatially variant PSF model where the PSF parameters were obtained by using point source images measured at 18 positions in the FOV and a spatial invariant PSF model where the PSF parameters were obtained by using only one image measured at center FOV. The performance of the image reconstruction method was evaluated by using simulated phantom data, and phantom and in-vivo mouse data acquired on the scanner. The results showed that the proposed reconstruction method provided better spatial resolution,higher contrast recovery coefficient and lower noise as compared to the OSEM reconstruction and was more than 1000 times faster than the CPU-based reconstruction. The spatially variant PSF model did not result in any spatial resolution improvement as compared to the spatial invariant PSF model, so the latter that is much easier to be implemented in image reconstruction can be used in small animal PET scanner using detectors with very high DOI resolution. Whole body 18F-FDG mouse image with high resolution and high contrast to noise ratio was obtained by using the proposed reconstruction method.

19.
J Affect Disord ; 274: 486-493, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32663980

RESUMO

BACKGROUND: Reduced plasma circular RNA DYM (circDYM) has been detected in patients with major depressive disorder (MDD). Mechanism research has demonstrated that circDYM, acting as a microRNA-9 sponge, suppressed microglial activation by increasing Heat Shock Protein 90 ubiquitination, indicating that circDYM could be a potential biomarker of MDD. METHODS: Thirty-two normal controls (NCs) and 60 MDD patients were recruited. Enrolled patients were randomly allocated to the real or sham repetitive transcranial magnetic stimulation (rTMS) group, followed by continuous five-day visual cortical rTMS or sham treatment. All participants underwent multidimensional neuropsychological assessments and detection of circDYM levels. RESULTS: Initial scores on all emotional and psychosocial assessments in MDD were significantly different from those of NCs. As compared with the NC group, baseline plasma circDYM levels in MDD patients decreased remarkably (p=0.030) and showed significant positive correlations with the scores of the 24-item Hamilton Depression Rating Scale (r=0.318, p=0.031) and retardation subscale (r=0.323, p=0.029). The increase in circDYM was noteworthy after rTMS (p=0.006), while downregulation with no statistical significance was observed after sham treatment (p=0.170). LIMITATIONS: It was not estimated on the correlation between plasma circDYM levels and long-term efficacy of rTMS. The mechanism of upregulated circDYM expression in response to visual cortical rTMS remained unrevealed, and the sample size was relatively small. CONCLUSIONS: This study verified the reduced circDYM levels in MDD patients, and further determined the upregulated circDYM expression after rTMS treatment, revealing the potential of circDYM as a biomarker for MDD diagnosis and antidepressant effect of visual cortical rTMS.

20.
Front Psychiatry ; 11: 446, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32581860

RESUMO

Objectives: Schizophrenia (SZ) is a complex psychiatric disorder that has a strong genetic basis. Dystrobrevin-binding protein 1 (DTNBP1) is one of the genes thought to be pivotal in regulating the glutamatergic system. Studies have suggested that variations in DTNBP1 confer susceptibility to SZ and clinical symptoms. Here, we performed a two-stage independent verification study to identify polymorphisms of the DTNBP1 gene that might be associated with SZ in the Han Chinese population. Methods: In stage 1, 14 single nucleotide polymorphisms (SNPs) were genotyped in 528 paranoid SZ patients and 528 healthy controls (HCs) using the Illumina GoldenGate assays on a BeadStation 500G Genotyping System. In stage 2, ten SNPs were genotyped in an independent sample of 1,031 SZ patients and 621 HCs using the Illumina 660k Genotyping System. Clinical symptoms were assessed using the Positive and Negative Syndrome Scale. Results: There was a significant association related to allele frequency, and a trend association in relation to genotype between SZ patients and HCs at rs4712253 (p = 0.03 and 0.05, respectively). These associations were not evident following Bonferroni correction (p > 0.05 for both). Haplotype association analysis revealed that only two haplotypes (GAG and GAA; rs16876575-rs9464793-rs4712253) were significantly different between SZ patients and HCs (χ2 = 4.24, 6.37, p = 0.04 and 0.01, respectively). In addition, in SZ patients there was a significant association in the rs4964793 genotype for positive symptoms, and in the rs1011313 genotype for excitement/hostility symptoms (p = 0.01 and 0.002, respectively). We found a significant association in the baseline symbol digital modalities test (SDMT), forward-digital span (DS), backward-DS, and semantic fluency between SZ patients and HCs (p < 0.05 for all). Finally, the SNP rs1011313 genotypes were associated with SDMT in SZ patients (p = 0.04). Conclusion: This study provides further evidence that SNP rs4712253 of DTNBP1 has a nominal association with SZ in the Han Chinese population. Such a genotype variation may play a role in psychopathology and cognitive function.

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