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1.
Physiol Behav ; : 112805, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31954148

RESUMO

Extracellular signal-regulated kinase (ERK) signal transduction is known to be associated with neurogenesis and neuronal differentiation and as such may be related to the synaptic plasticity associated with cognitive function. Although antipsychotic drug studies have suggested a potential role for the ERK cascade in schizophrenia, the mechanistic basis is unknown. The maternal immune activation (MIA) rat model is a well-known to simulate many of the clinical symptoms of schizophrenia, including cognitive deficits, but a role in this model for dynamic changes in ERK has not been established. In this study, polyinosinic:polycytidylic acid was administered to rats intravenously at a dose of 10 mg/kg on embryonic day 9.5 to produce MIA. The effect of MIA on behavior and ERK phosphorylation within the prefrontal cortex and the hippocampus of adolescent and adult offspring were explored. We also examined neurofilaments, a marker of neurogenesis, which have been reported to be modulated by ERK signaling. The results demonstrate an age- and region-specific profile of ERK expression and phosphorylation and suggest possible relationships among ERK, neurofilament expression, and cognitive performance in schizophrenia.

2.
Int J Cancer ; 146(1): 208-222, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31251822

RESUMO

The role of Fyn-related kinase (FRK) in malignant tumors remains controversial. Our study investigated the function of FRK in lung cancer. Immunohistochemistry staining and generating a knockout of FRK by CRISPR/Cas9 in H1299 (FRK-KO-H1299) cells were strategies used to explore the role of FRK. Immunohistochemistry staining indicated that FRK expression was elevated in 223 lung cancer tissues compared to 26 distant normal lung tissues. FRK contributed to poor survival status in lung cancer patients and acted as a predictor for poor prognosis of lung cancer. Knockout of FRK by CRISPR/Cas9 markedly inhibited proliferation, invasion, colony formation and epithelial-mesenchymal transition (EMT) process in the lung cancer cell line H1299. Further exploration indicated that FRK-KO damaged the stemness phenotype of H1299 by inhibiting CD44 and CD133 expression. Seahorse detection and a U-13 C flux assay revealed that FRK-KO induced metabolism reprogramming by inhibiting the Warburg effect and changing the energy type in H1299 cells. Epidermal growth factor stimulation recovered the expression of FRK and biological functions, metabolic reprogramming and stemness phenotype of H1299 cells. FRK plays an oncogenic role in lung cancer cells via a novel regulation mechanism of enhancing the stemness of H1299 cells by inducing metabolism reprogramming, which finally promotes EMT and metastasis. Our study also indicates that FRK could be used as a potential therapeutic target for drug development.

3.
Schizophr Res ; 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31784338

RESUMO

The default mode network (DMN), is one of the most popularly employed resting-state networks applied in schizophrenia (SCZ) research. However, the homogeneity of this network in adolescent-onset SCZ (AOS) remains unknown. This study aims to use network homogeneity (NH) to explore the functional connectivity in the DMN of AOS patients. Resting-state functional magnetic resonance imaging scans were used to study 48 drug-naïve, first-episode AOS patients and 31 healthy age, gender, and education matched control. An automatic NH approach was employed to analyze the imaging dataset. Our results revealed that the patients had significantly higher NH values in the left medial prefrontal cortex (MPFC), and significantly lower values in the bilateral posterior cingulate cortex/precuneus (PCC/PCu) than those in healthy controls. We performed the receiver operating characteristic curve analysis to show that NH values of the left superior MPFC might be regarded as a potential marker in helping to identify patients. In addition, negative associations were found regarding abnormal values of NH in the left PCC/PCu as well as in the Maze and Stroop color-word tests in patients. The outcomes showed abnormal NH values in the DMN of drug-naïve, first-episode AOS suggesting specific functions of the DMN in the pathophysiology of SCZ.

4.
Cancer Res ; 2019 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-31874856

RESUMO

The DNA damage response (DDR) is essential for maintaining genome integrity. Mounting evidence reveals that protein modifications play vital roles in the DDR. Here, we show that USP38 is involved in the DDR by regulating the activity of HDAC1. In response to DNA damage, USP38 interacted with HDAC1 and specifically removed the K63-linked ubiquitin chain promoting the deacetylase activity of HDAC1. As a result, HDAC1 was able to deacetylate H3K56. USP38 deletion resulted in persistent focal accumulation of NHEJ factors at DNA damage sites and impaired NHEJ efficiency, causing genome instability and sensitizing cancer cells to genotoxic insults. Knockout of USP38 rendered mice hypersensitive to IR and shortened survival. In addition, USP38 was expressed at low levels in certain types of cancers including renal cell carcinoma, indicating dysregulation of USP38 expression contributes to genomic instability and may lead to tumorigenesis. In summary, this study identifies a critical role of USP38 in modulating genome integrity and cancer cell resistance to genotoxic insults by deubiquitinating HDAC1 and regulating its deacetylation activity.

5.
Int J Biol Macromol ; 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31715236

RESUMO

Alzheimer's disease (AD) is the most common degenerative disease of the central nervous system. It is associated with abnormal accumulation of amyloid-ß (Aß) plaques, impaired neurogenesis, and damaged cognitive functions. We have known for a long time that natural compounds and their derivatives have gained increasing attention in AD drug research due to their multiple effects and inherently enormous chemicals. In this study, we will demonstrate that polysaccharides from L. barbarum (LBP1), a traditional natural compound, can reduce Aß level and improve the cognitive functions in APP/PS1 transgenic mouse. LBP1 can enhance neurogenesis as indicated by BrdU/NeuN double labeling. Furthermore, it can restore synaptic dysfunction at hippocampus CA3-CA1 pathway. Additionally, in vitro cell assay indicates that LBP1 may affect Aß processing. In conclusion, our study indicates that LBP1 might be a potential therapeutic agent for the treatment of AD against multiple targets that include synaptic plasticity, Aß pathology and neuropathology.

6.
Phys Med Biol ; 64(23): 23NT02, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31722318

RESUMO

PET scanners using SiPMs as photodetectors could have tens of thousands of SiPMs. To simplify the readout electronics, analog signal multiplexing readouts are always preferred to be used as early as possible. In this paper, two simple analog signal multiplexing readouts, a capacitive charge-division readout, and a resistive charge-division readout were evaluated and compared using dual-ended readout detectors based on 10 × 10 arrays of SensL MicroFJ-30035 SiPMs coupled to both ends of a 20 × 20 LYSO array with a pitch size of 1.5 mm and a length of 20 mm. The performance of the detectors were evaluated at different bias voltages (from 27.0 V to 30.5 V with an interval of 0.5 V) and a temperature of 22.8 °C. The flood histograms show that all the crystals in the LYSO array were clearly identified, whilst better flood histogram was obtained using the resistive charge-division readout. At a bias voltage of 29.5V, the flood histogram quality, energy resolution, DOI resolution, and timing resolution of the detector obtained using the capacitive charge-division readout were 3.28 ± 0.85, 18.9% ± 6.2%, 1.93 ± 0.20 mm, 1.25 ± 0.11 ns respectively, and those obtained using the resistive charge-division readout were 3.57 ± 0.81, 16.9% ± 6.5%, 1.96 ± 0.23 mm and 1.23 ± 0.07 ns, respectively. Overall, the detector with the resistive charge-division readout provided better performance.

7.
PeerJ ; 7: e7576, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31565561

RESUMO

Background: The increasing demand for food production has resulted in the use of large quantities of chemical fertilizers. This has created major environmental problems, such as increased ammonia volatilization, N2O emission, and nitrogen (N) leaching from agricultural soil. In particular, the utilization rate of N fertilizer is low in subtropical southern parts of China due to high rainfall. This causes not only large financial losses in agriculture, but also serious environmental pollution. Methods: In this study, 16S rDNA-based analysis and static-chamber gas chromatography were used to elucidate the effects of continuous straw biochar application on the N pool and bacteria environment in two typical soil types, purple and paddy soils, in southern China. Results: Straw biochar application (1) improved the soil N pool in both rhizosphere and non-rhizosphere soils; (2) significantly reduced the emission of N2O, with no difference in emission between 1 and 2 years of application; (3) increased the abundance of N-processing bacteria in the soil and altered the bacterial community structure; and (4) improved the tobacco yield and N use efficiency in paddy soil. These findings suggest that, in southern China, the application of straw biochar can promote N transformation in purple and paddy soils and reduce the emission of the greenhouse gas N2O.

8.
J Clin Transl Hepatol ; 7(3): 213-220, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31608212

RESUMO

Background and Aims: Ravidasvir (RDV) is a new generation pangenotypic hepatitis C virus (HCV) NS5A inhibitor, with high barrier to baseline resistance-associated species. This is the first phase 2/3 study conducted in Mainland China confirming the efficacy and safety of RDV + ritonavir-boosted danoprevir + ribavirin for 12 weeks in treatment-naïve noncirrhotic patients with genotype 1 infection in a large population. Methods: In this multicenter, randomized, double-blinded, placebo-controlled phase 2/3 trial (NCT03362814), we enrolled 424 treatment-naïve, noncirrhotic adult HCV genotype 1 patients. All patients were randomized at 3:1 ratio to receive a combination of RDV 200mg once daily plus ritonavir-boosted danoprevir 100mg/100mg twice daily and oral ribavirin 1000/1200mg/day (body weight <75/≥75 kg) (n = 318) or placebo (n = 106) for 12 weeks. The primary end-point was the rate of sustained virologic response 12 weeks after the end of treatment, and the safety was evaluated and compared between treatment and placebo groups. Results: The overall rate of sustained virological response at 12 weeks after treatment is 99% (306/309, 95%, CI: 97%-100%) under per protocol set analysis. All patients harboring baseline NS5A resistance-associated species in the treatment group (76/76, per protocol set) achieved sustained virological response at 12 weeks after treatment. No treatment-related serious adverse events were reported. Laboratory abnormalities showed mild or moderate severity (grade 1 and grade 2) in liver function tests. Conclusions: In treatment-naïve, noncirrhotic HCV Chinese patients infected with HCV genotype 1, all-oral regimen of RDV + ritonavir-boosted danoprevir + ribavirin for 12 weeks was highly efficacious, safe, and well tolerated.

9.
J Clin Transl Hepatol ; 7(3): 221-225, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31608213

RESUMO

Background and Aims: Genotype (GT) 1 remains the predominant hepatitis c virus (HCV) GT in Chinese patients. Over 80% of those Chinese patients harbor the interferon-sensitive CC allele of IFNL4rs12979860, which is favorable for interferon-based treatment regimens. This phase III clinical trial aimed to evaluate the efficacy and safety of the ritonavir-boosted danoprevir plus pegylated-interferon α-2a and ribavirin regimen for 12 weeks in treatment-naïve mainland Chinese patients infected with HCV GT1 without cirrhosis. Methods: One hundred and forty-one treatment-naïve, non-cirrhotic HCV GT1 Chinese patients (age ≥18 years) were enrolled for this single-arm, multicenter, phase III MANASA study (NCT03020082). Patients received a combination of ritonavir-boosted danoprevir (100 mg/100 mg) twice a day plus subcutaneous injection of weekly pegylated-interferon α-2a (180 µg) and oral ribavirin (1000/1200 mg/day body weight <75/≥75 kg) for 12 weeks. The primary end-point was sustained virologic response rate at 12 weeks after the end of treatment. The secondary end-points were safety outcomes, tolerability, virologic response over time and relapse rate. Results: All enrolled patients were HCV GT1-infected, and most among them (97.9%, 123/141) had the HCV GT1b subtype. Single-nucleotide polymorphism test showed that the majority of patients were of the IFNL4 rs12979860 CC genotype (87.2%, 123/141). Overall, 140 patients completed the 12-week treatment, and 97.1% (136/140) patients achieved sustained virologic response at 12 weeks (per protocol population group, 95% confidence interval: 92.9-99.2%). Only drug-related serious adverse event occurred. Most of the adverse events were grade 1 and grade 2 alanine aminotransferase elevation or liver dysfunction. One patient discontinued treatment because of severe head injury in a car accident. Conclusions: The triple regimen of ritonavir-boosted danoprevir plus pegylated-interferon α-2a and ribavirin produced a sustained virologic response rate of 97.1% after 12 weeks treatment in noncirrhotic HCV GT1-infected Chinese patients, and was safe and well tolerated. Trial Registration Clinical-Trials.gov Identifier: NCT03020082.

10.
BMC Plant Biol ; 19(1): 444, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31651252

RESUMO

BACKGROUND: The plant-specific homeodomain-leucine zipper class IV (HD-ZIP IV) gene family has been involved in the regulation of epidermal development. RESULTS: Fifteen genes coding for HD-ZIP IV proteins were identified (NtHD-ZIP-IV-1 to NtHD-ZIP-IV-15) based on the genome of N. tabacum. Four major domains (HD, ZIP, SAD and START) were present in these proteins. Tissue expression pattern analysis indicated that NtHD-ZIP-IV-1, - 2, - 3, - 10, and - 12 may be associated with trichome development; NtHD-ZIP-IV-8 was expressed only in cotyledons; NtHD-ZIP-IV-9 only in the leaf and stem epidermis; NtHD-ZIP-IV-11 only in leaves; and NtHD-ZIP-IV-15 only in the root and stem epidermis. We found that jasmonates may induce the generation of glandular trichomes, and that NtHD-ZIP-IV-1, - 2, - 5, and - 7 were response to MeJA treatment. Dynamic expression under abiotic stress and after application of phytohormones indicated that most NtHD-ZIP IV genes were induced by heat, cold, salt and drought. Furthermore, most of these genes were induced by gibberellic acid, 6-benzylaminopurine, and salicylic acid, but were inhibited by abscisic acid. NtHD-ZIP IV genes were sensitive to heat, but insensitive to osmotic stress. CONCLUSION: NtHD-ZIP IV genes are implicated in a complex regulatory gene network controlling epidermal development and abiotic stress responses. The present study provides evidence to elucidate the gene functions of NtHD-ZIP IVs during epidermal development and stress response.

11.
Anal Chim Acta ; 1086: 110-115, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31561785

RESUMO

Estrogen receptors (ERs) play a major role in the signaling pathways and participate in regulating and maintaining the basic activities of life. The abnormal expression of ERs has a significant effect on tumorigenesis. Herein, we propose an electrochemical method for detecting ERs based on the formation of DNA Y-Junction with a 3'-blunt end. The DNA Y-junction was designed to have one of its arms bound to an ER. When an ER was bound to the junction, which was immobilized on the electrode surface, it protected the DNA Y-junction from Exo III-catalyzed digestion. DNA Y-Junction also contained G-quadruplex rich duplex, which generated electrochemical signals when hemin was added to the electrode, resulting in the quantitative detection of ERs. The detection range of the ER using this method was 0.1-200 nM with a detection limit of 0.034 nM. Since this assay can be employed to detect ERs in tumor cells, it may be useful in tumor diagnosis in the future.

12.
Med Phys ; 46(11): 5014-5026, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31494950

RESUMO

PURPOSE: Positron emission tomography (PET) is an important tool for nuclear medical imaging. It has been widely used in clinical diagnosis, scientific research, and drug testing. PET is a kind of emission computed tomography. Its basic imaging principle is to use the positron annihilation radiation generated by radionuclide decay to generate gamma photon images. However, in practical applications, due to the low gamma photon counting rate, limited acquisition time, inconsistent detector characteristics, and electronic noise, measured PET projection data often contain considerable noise, which results in ill-conditioned PET images. Therefore, determining how to obtain high-quality reconstructed PET images suitable for clinical applications is a valuable research topic. In this context, this paper presents an image reconstruction algorithm based on patch-based regularization and dictionary learning (DL) called the patch-DL algorithm. Compared to other algorithms, the proposed algorithm can retain more image details while suppressing noise. METHODS: Expectation-maximization (EM)-like image updating, image smoothing, pixel-by-pixel image fusion, and DL are the four steps of the proposed reconstruction algorithm. We used a two-dimensional (2D) brain phantom to evaluate the proposed algorithm by simulating sinograms that contained random Poisson noise. We also quantitatively compared the patch-DL algorithm with a pixel-based algorithm, a patch-based algorithm, and an adaptive dictionary learning (AD) algorithm. RESULTS: Through computer simulations, we demonstrated the advantages of the patch-DL method over the pixel-, patch-, and AD-based methods in terms of the tradeoff between noise suppression and detail retention in reconstructed images. Quantitative analysis shows that the proposed method results in a better performance statistically [according to the mean absolute error (MAE), correlation coefficient (CORR), and root mean square error (RMSE)] in considered region of interests (ROI) with two simulated count levels. Additionally, to analyze whether the results among these methods have significant differences, we used one-way analysis of variance (ANOVA) to calculate the corresponding P values. The results show that most of the P < 0.01; some P> 0.01 < 0.05. Therefore, our method can achieve a better quantitative performance than those of traditional methods. CONCLUSIONS: The results show that the proposed algorithm has the potential to improve the quality of PET image reconstruction. Since the proposed algorithm was validated only with simulated 2D data, it still needs to be further validated with real three-dimensional data. In the future, we intend to explore GPU parallelization technology to further improve the computational efficiency and shorten the computation time.

13.
Phys Med Biol ; 64(20): 205004, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31530747

RESUMO

The probability of inter-crystal scattering (ICS) events for 511 keV gamma rays in all current scintillation crystals is high and the ICS events degrade the spatial resolution of PET scanners. In this work, Monte Carlo simulations were performed to study the effects of ICS events on the sensitivity and spatial resolution of PET detectors. LaBr3, LYSO, and PWO that represent scintillation crystals of low, medium and high density, respectively, were used. For a point source placed in the middle of two scintillation detectors of 50 × 50 × 20 mm3 and a lower energy threshold (LET) of 350 keV, the probabilities that at least one gamma ray undergoes ICS are 94%, 84% and 76% for LaBr3, LYSO, and PWO, respectively. The ICS events still provide useful spatial information. The full width at half maximum (FWHM), the full width at tenth maximum (FWTM) and the mean absolute error (MAE) of the curve of the mispositioning of a point source caused by ICS events are 0.45, 3.0 and 0.9 mm if the most popular PET scintillator LYSO is used. The MAE is smaller than the spatial resolution of most current PET scanners. The effect of ICS increases as the detector LET increases, scintillator density decreases, and crystal size decreases. The intrinsic spatial resolutions of a pair of LYSO detectors were calculated using curves of the coincidence counts between one column of the crystals in the two detectors and the sum of the coincidence counts between two opposite crystals of the columns in the two detectors that are in line with the point source changing with the source positions. The latter method removes almost all of ICS events. The FWHM (FWTM) intrinsic spatial resolutions obtained by the two methods are 0.40 (2.0) mm and 0.33 (0.8) mm if the crystal size is 0.5 mm, and are 0.8 (3.0) and 0.68 (1.5) mm if the crystal size is 1.0 mm. ICS events have much bigger contributions to the FWTM rather than the FWHM of the intrinsic spatial resolution of PET detectors. The spatial resolution of a PET scanner can still be improved by decreasing the crystal size to as small as 0.5 mm.

14.
J Viral Hepat ; 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31520460

RESUMO

A simple, pangenotypic and effective treatment regimen for patients with a broad range of chronic hepatitis C virus (HCV) infections remains an unmet medical need. We conducted a phase 2, randomized, open study involving untreated patients with chronic HCV genotypes 1, 2, 3, or 6 infections. Patients without cirrhosis were randomly assigned in a 1:2 ratio to receive capsules of the NS5A inhibitor coblopasvir at a dose of 30 or 60 mg plus tablets of the nucleotide polymerase inhibitor sofosbuvir (400 mg) once daily for 12 weeks. Patients with cirrhosis received 60 mg coblopasvir plus sofosbuvir for 12 weeks. The primary endpoint was the sustained virologic response at 12 weeks after the end of therapy (SVR12). Of the 110 patients who were enrolled in the study, 59 were male, 62.7% had HCV genotype 1, 24.5% had genotype 2, 6.4% had genotype 3, and 6.4% had genotype 6. The average age was 45.5 years. A total of 10.9% of patients had compensated cirrhosis. The rate of SVR12 was 98.2% in the intention-to-treat (ITT). One genotype 6 patient with cirrhosis experienced virologic relapse. One genotype 2 patient without cirrhosis failed to complete the follow-up and quit the study. Serious adverse events (SAEs) were reported in 2 patients and were not related to coblopasvir and sofosbuvir. Most adverse events (AEs) did not require treatment. Coblopasvir plus sofosbuvir taken once daily for 12 weeks provided high rates of sustained virologic response (SVR) and had a good safety profile among patients with HCV genotypes 1, 2, 3, or 6 infections, including those with compensated cirrhosis.

16.
J Xray Sci Technol ; 27(5): 949-963, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31381539

RESUMO

PURPOSE: To reduce the cost of positron emission tomography (PET) scanning systems, image reconstruction algorithms for low-sampled data have been extensively studied. However, the current method based on total variation (TV) minimization regularization nested in the maximum likelihood-expectation maximization (MLEM) algorithm cannot distinguish true structures from noise resulting losing some fine features in the images. Thus, this work aims to recover fine features lost in the MLEM-TV algorithm from low-sampled data. METHOD: A feature refinement (FR) approach previously developed for statistical interior computed tomography (CT) reconstruction is applied to PET imaging to recover fine features in this study. The proposed method starts with a constant initial image and the FR step is performed after each MLEM-TV iteration to extract the desired structural information lost during TV minimization. A feature descriptor is specifically designed to distinguish structure from noise and artifacts. A modified steepest descent method is adopted to minimize the objective function. After evaluating the impacts of different patch sizes on the outcome of the presented method, an optimal patch size of 7×7 is selected in this study to balance structure-detection ability and computational efficiency. RESULTS: Applying MLEM-TV-FR algorithm to the simulated brain PET imaging using an emission activity phantom, a standard Shepp-Logan phantom, and mouse results in the increased peak signal-to-noise ratio (PSNR) and structural similarity (SSIM) as comparing to using the conventional MLEM-TV algorithm, as well as the substantial reduction of the used sampling numbers, which improves the computational efficiency. CONCLUSIONS: The presented algorithm can achieve image quality superior to that of the MLEM and MLEM-TV approaches in terms of the preservation of fine structure and the suppression of undesired artifacts and noise, indicating its useful potential for low-sampled data in PET imaging.

17.
Acta Pharm Sin B ; 9(4): 769-781, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31384537

RESUMO

Bicyclol is a synthetic drug for hepatoprotection in clinic since 2004. Preliminary clinical observations suggest that bicyclol might be active against hepatitis C virus (HCV) with unknown mechanism. Here, we showed that bicyclol significantly inhibited HCV replication in vitro and in hepatitis C patients. Using bicyclol as a probe, we identified glycolipid transfer protein (GLTP) to be a novel restrictive factor for HCV replication. The GLTP preferentially bound host vesicle-associated membrane protein-associated protein-A (VAP-A) in competition with the HCV NS5A, causing an interruption of the complex formation between VAP-A and HCV NS5A. As the formation of VAP-A/NS5A complex is essential for viral RNA replication, up-regulation of GLTP by bicyclol reduced the level of VAP-A/NS5A complex and thus inhibited HCV replication. Bicyclol also exhibited an inhibition on HCV variants resistant to direct-acting antiviral agents (DAAs) with an efficacy identical to that on wild type HCV. In combination with bicyclol, DAAs inhibited HCV replication in a synergistic fashion. GLTP appears to be a newly discovered host restrictive factor for HCV replication, Up-regulation of GLTP causes spontaneous restriction of HCV replication.

18.
EBioMedicine ; 47: 543-552, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31420302

RESUMO

BACKGROUND: Current fMRI-based classification approaches mostly use functional connectivity or spatial maps as input, instead of exploring the dynamic time courses directly, which does not leverage the full temporal information. METHODS: Motivated by the ability of recurrent neural networks (RNN) in capturing dynamic information of time sequences, we propose a multi-scale RNN model, which enables classification between 558 schizophrenia and 542 healthy controls by using time courses of fMRI independent components (ICs) directly. To increase interpretability, we also propose a leave-one-IC-out looping strategy for estimating the top contributing ICs. FINDINGS: Accuracies of 83·2% and 80·2% were obtained respectively for the multi-site pooling and leave-one-site-out transfer classification. Subsequently, dorsal striatum and cerebellum components contribute the top two group-discriminative time courses, which is true even when adopting different brain atlases to extract time series. INTERPRETATION: This is the first attempt to apply a multi-scale RNN model directly on fMRI time courses for classification of mental disorders, and shows the potential for multi-scale RNN-based neuroimaging classifications. FUND: Natural Science Foundation of China, the Strategic Priority Research Program of the Chinese Academy of Sciences, National Institutes of Health Grants, National Science Foundation.

19.
Front Psychiatry ; 10: 522, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31396115

RESUMO

Background: Altered resting-state functional connectivity of the cerebellum in obsessive-compulsive disorder (OCD) has been previously reported. However, the previous study investigating cerebellar-cerebral functional connectivity relied on a priori-defined seeds from specific networks. In this study, we aimed to explore the connectivity alterations of the cerebellum in OCD under resting-state conditions with a hypothesis-free approach. Methods: Thirty patients with OCD and 26 healthy controls (HCs) underwent functional magnetic resonance imaging (fMRI) scanning at resting state. Regional cerebral function was evaluated by measuring the fraction of amplitude of low-frequency fluctuation (fALFF). Regions with mean fALFF (mfALFF) alterations were used as seeds in seed correlation analysis (SCA). An independent samples t test was used to compare the differences in mfALFF and functional connection (FC) between the two groups. Pearson correlation analysis was performed to identify the association between functional neural correlates and OCD symptom severity evaluated using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Results: Compared with the HC group, the OCD group showed significantly increased mfALFF values in bilateral cerebellar. The results of FC analysis showed weakened connectivity among the left Crus II, lobule VIII, and right striatum and between the right lobule VIII and the right striatum, and cingulate in the OCD group compared with the HC group. Some of the abovementioned results were associated with symptom severity. Conclusions: OCD patients showed abnormal spontaneous cerebellar activity and weakened functional connectivity between the cerebellum and the cortico-striato-thalamo-cortical (CSTC) circuit (striatum and cingulate), suggesting that the cerebellum may play an essential role in the pathophysiology of OCD.

20.
J Xray Sci Technol ; 27(4): 739-753, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31227684

RESUMO

X-ray radiation is harmful to human health. Thus, obtaining a better reconstructed image with few projection view constraints is a major challenge in the computed tomography (CT) field to reduce radiation dose. In this study, we proposed and tested a new algorithm that combines penalized weighted least-squares using total generalized variation (PWLS-TGV) and dictionary learning (DL), named PWLS-TGV-DL to address this challenge. We first presented and tested this new algorithm and evaluated it through both data simulation and physical experiments. We then analyzed experimental data in terms of image qualitative and quantitative measures, such as the structural similarity index (SSIM) and the root mean square error (RMSE). The experiments and data analysis indicated that applying the new algorithm to CT data recovered images more efficiently and yielded better results than the traditional CT image reconstruction approaches.

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