Radiotherapy is increasingly used in the treatment of joint diseases, but limited information is available on the effects of radiation on cartilage. Here, we characterize the molecular mechanisms ...leading to cellular senescence in irradiated primary cultured articular chondrocytes. Ionizing radiation (IR) causes activation of ERK, in turn generating intracellular reactive oxygen species (ROS) with induction of senescence-associated β-galactosidase (SA-β-gal) activity. ROS activate p38 kinase, which further promotes ROS generation, forming a positive feedback loop to sustain ROS-p38 kinase signaling. The ROS inhibitors, nordihydroguaiaretic acid and GSH, suppress phosphorylation of p38 and cell numbers positive for SA-β-gal following irradiation. Moreover, inhibition of the ERK and p38 kinase pathways leads to blockage of IR-induced SA-β-gal activity via reduction of ROS generation. Although JNK is activated by ROS, this pathway is not associated with cellular senescence of chondrocytes. Interestingly, IR triggers down-regulation of SIRT1 protein expression but not the transcript level, indicative of post-transcriptional cleavage of the protein. SIRT1 degradation is markedly blocked by SB203589 or MG132 after IR treatment, suggesting that cleavage occurs as a result of binding with p38 kinase, followed by processing via the 26 S proteasomal degradation pathway. Overexpression or activation of SIRT1 significantly reduces the IR-induced senescence phenotype, whereas inhibition of SIRT1 activity induces senescence. Based on these findings, we propose that IR induces cellular senescence of articular chondrocytes by negative post-translational regulation of SIRT1 via ROS-dependent p38 kinase activation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Anatomically terminal parts of the urinary, reproductive, and digestive systems of birds all connect to the cloaca. As the feces drain through the cloaca in chickens, the cloacal bacteria were ...previously believed to represent those of the digestive system. To investigate similarities between the cloacal microbiota and the microbiota of the digestive and reproductive systems, microbiota inhabiting the colon, cloaca, and magnum, which is a portion of the chicken oviduct of 34-week-old, specific-pathogen-free hens were analyzed using a 16S rRNA metagenomic approach using the Ion torrent sequencer and the Qiime2 bioinformatics platform. Beta diversity via unweighted and weighted unifrac analyses revealed that the cloacal microbiota was significantly different from those in the colon and the magnum. Unweighted unifrac revealed that the cloacal microbiota was distal from the microbiota in the colon than from the microbiota in the magnum, whereas weighted unifrac revealed that the cloacal microbiota was located further away from the microbiota in the magnum than from the microbiota inhabiting the colon. Pseudomonas spp. were the most abundant in the cloaca, whereas Lactobacillus spp. and Flavobacterium spp. were the most abundant species in the colon and the magnum. The present results indicate that the cloaca contains a mixed population of bacteria, derived from the reproductive, urinary, and digestive systems, particularly in egg-laying hens. Therefore, sampling cloaca to study bacterial populations that inhabit the digestive system of chickens requires caution especially when applied to egg-laying hens. To further understand the physiological role of the microbiota in chicken cloaca, exploratory studies of the chicken's cloacal microbiota should be performed using chickens of different ages and types.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Herein, an Au‐coating layer adjusted on the surface of a Zn metal electrode that effectively suppresses the dendrite growth as well as the mechanisms underlying the dendrite suppression as a result ...of the zincophilic character of Au is introduced. For the Au‐coated Zn metal symmetric cell, uniform deposition of Zn‐derived compounds was revealed by operando synchrotron tomography. Microscopic studies demonstrate that the Au‐coating layer is induced to form a new Zn–Au alloy during the initial Zn deposition, resulting in stabilized long‐term stripping/plating of Zn via the ‘embracing effect’ that intimately accommodates Zn deposition for further cycles. This property supports the successful operation of symmetrical cells up to 50 mA cm−2. According to Zn electrodeposition simulation, it is verified that the suppression of dendrite growth is responsible for the electro‐conducting Au nanolayer that uniformly distributes the electric field and protects the Zn electrode from corrosion, ultimately promoting uniform Zn growth. The compatibility of the Au‐coating layer for full cell configuration is verified using NaV3O8 as a cathode material over 1 000 cycles. This finding provides a new pathway for the enhancement of the electrochemical performance of ZIBs by suppressing the dendritic growth of Zn by means of a zincophilic Au nanolayer.
From the initial Zn deposition, a Zn‐Au alloy grows from the Au‐coating layer. This further results in smooth Zn deposition, which stabilizes long‐term Zn stripping/plating without Zn dendrite via the ‘embracing effect’.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
All metazoan guts are in permanent contact with the microbial realm. However, understanding of the exact mechanisms by which the strength of gut immune responses is regulated to achieve gut-microbe ...mutualism is far from complete. Here we identify a signaling network composed of complex positive and negative mechanisms that controlled the expression and activity of dual oxidase (DUOX), which 'fine tuned' the production of microbicidal reactive oxygen species depending on whether the gut encountered infectious or commensal microbes. Genetic analyses demonstrated that negative and positive regulation of DUOX was required for normal host survival in response to colonization with commensal and infectious microbes, respectively. Thus, the coordinated regulation of DUOX enables the host to achieve gut-microbe homeostasis by efficiently combating infection while tolerating commensal microbes.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Normal pressure hydrocephalus (NPH) patients had altered white matter tract integrities on diffusion tensor imaging (DTI). Previous studies suggested disproportionately enlarged subarachnoid space ...hydrocephalus (DESH) as a prognostic sign of NPH. We examined DTI indices in NPH subgroups by DESH severity and clinical symptoms. This retrospective case-control study included 33 NPH patients and 33 age-, sex-, and education-matched controls. The NPH grading scales (0-12) were used to rate neurological symptoms. Patients with NPH were categorized into two subgroups, high-DESH and low-DESH groups, by the average value of the DESH scale. DTI indices, including fractional anisotropy, were compared across 14 regions of interest (ROIs). The high-DESH group had increased axial diffusivity in the lateral side of corona radiata (1.43 ± 0.25 vs. 1.72 ± 0.25, p = 0.04), and showed decreased fractional anisotropy and increased mean, and radial diffusivity in the anterior and lateral sides of corona radiata and the periventricular white matter surrounding the anterior horn of lateral ventricle. In patients with a high NPH grading scale, fractional anisotropy in the white matter surrounding the anterior horn of the lateral ventricle was significantly reduced (0.36 ± 0.08 vs. 0.26 ± 0.06, p = 0.03). These data show that DESH may be a biomarker for DTI-detected microstructural alterations and clinical symptom severity.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Objective
Cerebral microbleeds (CMBs) are a neuroimaging marker of small vessel disease (SVD) with relevance for understanding disease mechanisms in cerebrovascular disease, cognitive impairment, and ...normal aging. It is hypothesized that lobar CMBs are due to cerebral amyloid angiopathy (CAA) and deep CMBs are due to subcortical ischemic SVD. We tested this hypothesis using structural magnetic resonance imaging (MRI) markers of subcortical SVD and in vivo imaging of amyloid in patients with cognitive impairment.
Methods
We included 226 patients: 89 with Alzheimer disease–related cognitive impairment (ADCI) and 137 with subcortical vascular cognitive impairment (SVCI). All subjects underwent amyloid imaging with 11C Pittsburgh compound B (PiB) positron emission tomography, and MRI to detect CMBs and markers of subcortical SVD, including the volume of white matter hyperintensities (WMH) and the number of lacunes.
Results
Parietal and occipital lobar CMBs counts were higher in PiB+ ADCI with moderate WMH than PiB+ ADCI with minimal WMH, whereas PiB− patients with SVCI (ie, “pure” SVCI) showed both lobar and deep CMBs. In multivariate analyses of the whole cohort, WMH volume and lacuna counts were positively associated with both lobar and deep CMBs, whereas amyloid burden (PiB) was only associated with lobar CMBs. There was an interaction between lacuna burden and PiB retention on lobar (but not deep) CMBs (p<0.001).
Interpretation
Our findings suggest that although deep CMBs are mainly linked to subcortical SVD, both subcortical SVD and amyloid‐related pathologies (eg, CAA) contribute to the pathogenesis of lobar CMBs, at least in subjects with mixed lobar and deep CMBs. Furthermore, subcortical SVD and amyloid‐related pathologies interact to increase the risk of lobar CMBs. Ann Neurol 2013;73:584–593
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background and Aim
Decreased kidney function is a putative risk factor for various cancers. However, few studies have investigated the association between a decreased estimated glomerular filtration ...rate (eGFR) and incident pancreatic cancer. We aimed to investigate the risk of incident pancreatic cancer according to eGFR categories.
Methods
In this retrospective cohort study, we included 359 721 adults who underwent health checkups in 2009 or 2010 by using the Korean National Health Insurance Database. The study population was categorized into four groups by eGFR (mL/min/1.73 m2) using the Chronic Kidney Disease Epidemiology Collaboration equation: group 1 (eGFR < 45), group 2 (eGFR ≥ 45 to < 60), group 3 (eGFR ≥ 60 to < 90), and group 4 (eGFR ≥ 90). Multivariate Cox proportional hazards models were used to determine the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the incidence of pancreatic cancer until 2019 by comparing the eGFR groups.
Results
During the 3 493 589.05 person‐years of follow‐up, 1702 pancreatic cancer cases were identified. Compared with group 4 (eGFR ≥ 90), HRs and 95% CIs for the incidence of pancreatic cancer were 1.39 (1.24–1.56) for group 3 (eGFR ≥ 60 to < 90), 1.79 (1.47–2.16) for group 2 (eGFR ≥ 45 to < 60), and 2.05 (1.62–2.60) for group 1 (eGFR < 45) in the multivariate adjusted model.
Conclusions
Decreased eGFR was significantly associated with an increased risk of pancreatic cancer in Korean population. Further studies are needed to investigate the relationship between a decreased eGFR and the risk of pancreatic cancer in other ethnic groups.
In Korean population, lower eGFR was associated with an increased risk of pancreatic cancer.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Electrochromic devices (ECDs) are emerging as a novel technology for various applications like commercialized smart window glasses, and auto-dimming rear-view mirrors. Recently, the development of ...low-power, lightweight, flexible, and stretchable devices has been accelerated to meet the growing demand in the new wearable devices market. Silver nanowires (AgNWs) can become new primary transparent conducting electrode (TCE) materials to replace indium tin oxide (ITO) for ECDs. However, issues such as substrate adhesion, delamination, and higher resistance still exist with AgNWs. Herein, we report a high-performance stretchable flash-induced AgNW-network-based TCE on surface-treated polydimethylsiloxane (PDMS) substrates. A Xe flash light method was used to create nanowelded networks of AgNWs. Surface silane treatments increased the adhesion and durability of the films as well. Finally, ECDs were fabricated under the optimal conditions and examined under strained conditions to demonstrate the resistance and mechanical behaviours of the devices. Results showed a flexible and durable film maintaining a high level of conductivity and reversible resistance behaviour, beyond those currently achievable with standard ITO/PET flexible TCEs.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Objectives
Deep learning (DL) has been increasingly employed for automated landmark detection, e.g., for cephalometric purposes. We performed a systematic review and meta-analysis to assess the ...accuracy and underlying evidence for DL for cephalometric landmark detection on 2-D and 3-D radiographs.
Methods
Diagnostic accuracy studies published in 2015-2020 in Medline/Embase/IEEE/arXiv and employing DL for cephalometric landmark detection were identified and extracted by two independent reviewers. Random-effects meta-analysis, subgroup, and meta-regression were performed, and study quality was assessed using QUADAS-2. The review was registered (PROSPERO no. 227498).
Data
From 321 identified records, 19 studies (published 2017–2020), all employing convolutional neural networks, mainly on 2-D lateral radiographs (n=15), using data from publicly available datasets (n=12) and testing the detection of a mean of 30 (SD: 25; range.: 7–93) landmarks, were included. The reference test was established by two experts (n=11), 1 expert (n=4), 3 experts (n=3), and a set of annotators (n=1). Risk of bias was high, and applicability concerns were detected for most studies, mainly regarding the data selection and reference test conduct. Landmark prediction error centered around a 2-mm error threshold (mean; 95% confidence interval: (–0.581; 95 CI: –1.264 to 0.102 mm)). The proportion of landmarks detected within this 2-mm threshold was 0.799 (0.770 to 0.824).
Conclusions
DL shows relatively high accuracy for detecting landmarks on cephalometric imagery. The overall body of evidence is consistent but suffers from high risk of bias. Demonstrating robustness and generalizability of DL for landmark detection is needed.
Clinical significance
Existing DL models show consistent and largely high accuracy for automated detection of cephalometric landmarks. The majority of studies so far focused on 2-D imagery; data on 3-D imagery are sparse, but promising. Future studies should focus on demonstrating generalizability, robustness, and clinical usefulness of DL for this objective.
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CMK, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Purpose
Although most deep learning (DL) studies have reported excellent classification accuracy, these studies usually target typical Alzheimer’s disease (AD) and normal cognition (NC) for which ...conventional visual assessment performs well. A clinically relevant issue is the selection of high-risk subjects who need active surveillance among equivocal cases. We validated the clinical feasibility of DL compared with visual rating or quantitative measurement for assessing the diagnosis and prognosis of subjects with equivocal amyloid scans.
Methods
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F-florbetaben scans of 430 cases (85 NC, 233 mild cognitive impairment, and 112 AD) were assessed through visual rating-based, quantification-based, and DL-based methods. DL was trained using 280 two-dimensional PET images (80%) and tested by randomly assigning the remaining (70 cases, 20%) cases and a clinical validation set of 54 equivocal cases. In the equivocal cases, we assessed the agreement among the visual rating, quantification, and DL and compared the clinical outcome according to each modality-based amyloid status.
Results
The visual reading was positive in 175 cases, equivocal in 54 cases, and negative in 201 cases. The composite SUVR cutoff value was 1.32 (AUC 0.99). The subject-level performance of DL using the test set was 100%. Among the 54 equivocal cases, 37 cases were classified as positive (Eq(deep+)) by DL, 40 cases were classified by a second-round visual assessment, and 40 cases were classified by quantification. The DL- and quantification-based classifications showed good agreement (83%,
κ
= 0.59). The composite SUVRs differed between Eq(deep+) (1.47 0.13) and Eq(deep−) (1.29 0.10;
P
< 0.001). DL, but not the visual rating, showed a significant difference in the Mini-Mental Status Examination score change during the follow-up between Eq(deep+) (− 4.21 0.57) and Eq(deep−) (− 1.74 0.76;
P
= 0.023) (mean duration, 1.76 years).
Conclusions
In visually equivocal scans, DL was more related to quantification than to visual assessment, and the negative cases selected by DL showed no decline in cognitive outcome. DL is useful for clinical diagnosis and prognosis assessment in subjects with visually equivocal amyloid scans.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
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