49 research outputs found
MRI-based prostate cancer detection with high-level representation and hierarchical classification
Extracting the high-level feature representation by using deep neural networks for detection of prostate cancer, and then based on high-level feature representation constructing hierarchical classification to refine the detection results
The chaos in calibrating crop models
Calibration, the estimation of model parameters based on fitting the model to experimental data, is among the first steps in many applications of system models and has an important impact on simulated values. Here we propose and illustrate a novel method of developing guidelines for calibration of system models. Our example is calibration of the phenology component of crop models. The approach is based on a multi-model study, where all teams are provided with the same data and asked to return simulations for the same conditions. All teams are asked to document in detail their calibration approach, including choices with respect to criteria for best parameters, choice of parameters to estimate and software. Based on an analysis of the advantages and disadvantages of the various choices, we propose calibration recommendations that cover a comprehensive list of decisions and that are based on actual practices.HighlightsWe propose a new approach to deriving calibration recommendations for system modelsApproach is based on analyzing calibration in multi-model simulation exercisesResulting recommendations are holistic and anchored in actual practiceWe apply the approach to calibration of crop models used to simulate phenologyRecommendations concern: objective function, parameters to estimate, software usedCompeting Interest StatementThe authors have declared no competing interest
Glut9-mediated Urate Uptake Is Responsible for Its Protective Effects on Dopaminergic Neurons in Parkinson’s Disease Models
Considerable evidence has shown that elevated plasma or cerebrospinal fluid (CSF) urate levels correlated with a reduced risk of Parkinson’s disease (PD). Based on its anti-oxidative properties, urate might serve as one of promising neuroprotective candidates for PD. However, how urate is transported through cell membranes to exert its effects inside the cells in PD is largely unknown. To elucidate this, we showed that increased intracellular urate exerted its neuroprotective effects against 1-methyl-4-phenylpyridinium (MPP+)-induced neurotoxicity in MES23.5 cells and elevated urate could antagonize 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced nigral dopaminergic neuronal death in urate oxidase (UOx) knockout (KO) mice. Its transporter, glucose transporter type 9 (Glut9), was observed up-regulated, which was caused by the activation of p53. These protective effects could be abolished by Glut9 blocker and p53 inhibitor. These results suggested that Glut9 was a functional urate transporter, whose up-regulation by activation of p53 resulted in the increased intracellular urate levels in PD models. Our findings suggest that Glut9 could be modified to modulate urate levels in dopaminergic neurons and urate-elevating strategies without increasing systemic levels to avoid side effects might serve as a potential therapeutic target for PD
Investigation of Behavioral Dysfunctions Induced by Monoamine Depletions in a Mouse Model of Parkinson's Disease
Parkinson's disease (PD) is characterized not only by typical motor symptoms, but also by nonmotor symptoms in the early stages. In addition to the loss of dopaminergic (DAergic) neurons, progressive degenerations of noradrenergic (NA) and serotonergic (5-HT) neurons were also observed. However, the respective effects and interactions of these monoamine depletions on certain nonmotor symptoms are still largely unknown. In the present study, we performed selective depletions of NA, 5-HT and DA in mice by intraperitioneal injection of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP-4), 4-chloro-L-phenylalanine (pCPA) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), respectively. DSP-4 led to a 34% decrease in the number of NAergic neurons in the locus coeruleus, and MPTP led to a 30% decrease in the number of DAergic neurons in the substantia nigra. Although there was no obvious change in the number of 5-HTergic neurons in the dorsal raphe nucleus after pCPA treatment, the levels of 5-HT and its metabolite in the frontal cortex and hippocampus were reduced, respectively. Locomotor activity deficit was induced by DA depletion and a decrease in traveled distance was potentiated by additional NA depletion. Despair-associated depressive-like behavior could be observed in every group. Anxiety states emerged only from the combined depletion of two or three monoamines. However, combined depletion of the three monoamines dramatically induced anhedonia, and it could also aggravate the depressive-like and anxiety behavior. Furthermore, NA depletion significantly reduced spatial learning and memory ability, which was not enhanced by additional 5-HT or DA depletion. Our data highlighted the interactive role of NA, 5-HT and DA in the motor, emotional and cognitive deficits, providing new insight into the complex orchestration of impaired monoaminergic systems that related to the pathology of PD
Discriminating Active Tuberculosis from Latent Tuberculosis Infection by flow cytometric measurement of CD161-expressing T cells
Interferon-gamma Release Assays (IGRAs) significantly increases the possibility for early diagnosis of tuberculosis, but IGRAs alone cannot discriminate active TB from LTBI. Therefore, fast and reliable discrimination of active tuberculosis, especially bacteriology negative tuberculosis, from LTBI is a great necessity. Here we established an assay based on flow cytometric multiparameter assay assessing expression of CD161 along with CD3, CD4, and CD8, whereby a set of indices formulated by the percentages of CD3(+)CD161(+), CD3(+)CD4(+)CD161(+) and CD3(+)CD8(+)CD161(+) T cells multiplied with lymphocyte/monocyte ratio were established. Application of the CD3(+)CD8(+)CD161(+) index to compare a cohort of active tuberculosis with a cohort of LTBI or health control yielded 0.7662 (95% confidence interval [CI] 0.6559-0.8552) or 0.7922 (95% CI 0.6846-0.8763) for sensitivity and 0.9048 (95% CI 0.8209-0.9580) or 0.8939 (95% CI 0.8392-0.9349) for specificity when the TB cohort was AFB(+); the corresponding results were 0.7481 (95% CI 0.6648-0.8198) or 0.7557 (95% CI 0.6730-0.8265) for sensitivity and 0.8571 (95% CI 0.7637-0.9239) or 0.8603 (95% CI 0.8008-0.9075) for specificity when the TB cohort was AFB(-). Our results reveal that in combination with IGRAs, CD161-based indices provide a novel, fast diagnostic solution addressing the limitation of current tuberculosis diagnostics
Effects of surgery versus radiotherapy in patients with localized prostate cancer in terms of urinary, bowel, and sexual domains
Abstract Background The health‐related quality of life (HRQoL) of patients with localized prostate cancer (LPCa) after treatment mainly surgery and radiotherapy (RT) has received increasing attention. The aim of this study is to compare the HRQoL of LPCa after surgery and RT. Methods Web of Science, Embase, PubMed and Cochrane databases were searched after January 2000 to observe the HRQoL scores after surgery and RT at different treatment time points. Results A total of 28 studies were included in this study, and the results showed that LPCa received surgery had better bowel scores than RT at ≤3 (weighted mean differences [WMD] = 4.18; p = 0.03), 3–6 (WMD = 4.16; p < 0.001), 6–12 (WMD = 2.99; p = 0.004), 24–60 (WMD = 1.87; p = 0.06), and ≥60 (WMD = 4.54; p = 0.02) months. However, LPCa received RT had higher urinary scores at ≤3 (WMD = −7.39; p = 0.02), 3–6 (WMD = −6.03; p = 0.02), 6–12 (WMD = −4.90; p < 0.001), 24–60 (WMD = −3.96; p < 0.001), ≥60 (WMD = −2.95; p < 0.001) months and had better sexual scores at ≤3 (WMD = −13.58; p = 0.09), 3–6 (WMD = −12.32; p = 0.06), 6–12 (WMD = −12.03; p = 0.002), 24–60 (WMD = −11.29; p < 0.001), and ≥60 (WMD = −3.10; p = 0.46) months than surgery. The scores difference between surgery and RT decreased over time. Conclusion Overall, for LPCa, surgery was associated with better HRQoL in the bowel domain, whereas RT was associated with better HRQoL in the urinary and sexual domains, with the difference between surgery and RT narrowing over time
Deep-Learning-Based Automatic Extraction of Aquatic Vegetation from Sentinel-2 Images—A Case Study of Lake Honghu
Aquatic vegetation is an important component of aquatic ecosystems; therefore, the classification and mapping of aquatic vegetation is an important aspect of lake management. Currently, the decision tree (DT) classification method based on spectral indices has been widely used in the extraction of aquatic vegetation data, but the disadvantage of this method is that it is difficult to fix the threshold value, which, in turn, affects the automatic classification effect. In this study, Sentinel-2 MSI data were used to produce a sample set (about 930 samples) of aquatic vegetation in four inland lakes (Lake Taihu, Lake Caohai, Lake Honghu, and Lake Dongtinghu) using the visual interpretation method, including emergent, floating-leaved, and submerged vegetation. Based on this sample set, a DL model (Res-U-Net) was used to train an automatic aquatic vegetation extraction model. The DL model achieved a higher overall accuracy, relevant error, and kappa coefficient (90%, 8.18%, and 0.86, respectively) compared to the DT method (79%, 23.07%, and 0.77) and random forest (78%,10.62% and 0.77) when utilizing visual interpretation results as the ground truth. When utilizing measured point data as the ground truth, the DL model exhibited accuracies of 59%, 78%, and 91% for submerged, floating-leaved, and emergent vegetation, respectively. In addition, the model still maintains good recognition in the presence of clouds with the influence of water bloom. When applying the model to Lake Honghu from January 2017 to October 2023, the obtained temporal variation patterns in the aquatic vegetation were consistent with other studies. The study in this paper shows that the proposed DL model has good application potential for extracting aquatic vegetation data
Deubiquitylase OTUD3 Mediates Endoplasmic Reticulum Stress through Regulating Fortilin Stability to Restrain Dopaminergic Neurons Apoptosis
OTU domain-containing protein 3 (OTUD3) knockout mice exhibited loss of nigral dopaminergic neurons and Parkinsonian symptoms. However, the underlying mechanisms are largely unknown. In this study, we observed that the inositol-requiring enzyme 1α (IRE1α)-induced endoplasmic reticulum (ER) stress was involved in this process. We found that the ER thickness and the expression of protein disulphide isomerase (PDI) were increased, and the apoptosis level was elevated in the dopaminergic neurons of OTUD3 knockout mice. These phenomena were ameliorated by ER stress inhibitor tauroursodeoxycholic acid (TUDCA) treatment. The ratio of p-IRE1α/IRE1α, and the expression of X-box binding protein 1-spliced (XBP1s) were remarkably increased after OTUD3 knockdown, which was inhibited by IRE1α inhibitor STF-083010 treatment. Moreover, OTUD3 regulated the ubiquitination level of Fortilin through binding with the OTU domain. OTUD3 knockdown resulted in a decrease in the interaction ability of IRE1α with Fortilin and finally enhanced the activity of IRE1α. Taken together, we revealed that OTUD3 knockout-induced injury of dopaminergic neurons might be caused by activating IRE1α signaling in ER stress. These findings demonstrated that OTUD3 played a critical role in dopaminergic neuron neurodegeneration, which provided new evidence for the multiple and tissue-dependent functions of OTUD3
CDK12 loss inhibits cell proliferation by regulating TBK1 in non-small cell lung cancer cells
Lung cancer is one of the most common malignant tumors and has a poor prognosis and a low survival rate. Traditional treatments, such as radiotherapy and chemotherapy, still face some challenges because of high drug resistance and toxicity. Therefore, it is necessary to discover a new kind of targeted drug with low toxicity and high efficiency. CDK12 is a cell cycle-dependent kinase whose main function is to activate RNA polymerase II (RNAPII) and promote the transcriptional extension of RNA. However, the role and molecular mechanism of CDK12 in lung cancer are still unclear.In this study, the mutation and RNA-Seq data of CDK12 in lung adenocarcinoma and squamous cell carcinoma were downloaded from The Cancer Genome Atlas (TCGA) database and analyzed with the custom scripts. Cell proliferation was evaluated by Cell Counting Kit-8 (CCK-8) and cell colony formation assays. A subcutaneous tumor experiment in nude mice was used to examine the effects of CDK12 knockdown on the in vivo tumor growth of NSCLC cells. The cell cycle distribution and the apoptosis rate of lung cancer cells were assessed by flow cytometry. Regulation of TANK-binding kinase 1 (TBK1) by CDK12 was evaluated by quantitative PCR, immunoprecipitation and Western blot analysis.In this study we have analyzed the mutation and expression data of The Cancer Genome Atlas (TCGA) database and found that CDK12 is highly expressed in lung cancer tissues. Clinical correlation analysis showed that high expression of CDK12 in NSCLC reduces patient survival, but its high expression is only related to early tumor progression and has no significant correlation with late tumor progression and metastasis. Furthermore, we present evidence that CDK12 depletion in lung cancer cell lines not only leads to the inhibition of cell growth and induces apoptosis but also inhibits tumor growth of NSCLC cells in vivo. CDK12 positively regulates the expression of the oncogene TBK1 in lung cancer cells. These results revealed that CDK12 affects the progression of non-small cell lung cancer through positive regulation of TBK1 expression, suggesting that CDK12 might be a potential molecular target for the treatment of non-small cell lung cancer