Sensing and clearance of dysfunctional lysosomes is critical for cellular homeostasis. Here we show that transcription factor EB (TFEB)-a master transcriptional regulator of lysosomal biogenesis and ...autophagy-is activated during the lysosomal damage response, and its activation is dependent on the function of the ATG conjugation system, which mediates LC3 lipidation. In addition, lysosomal damage triggers LC3 recruitment on lysosomes, where lipidated LC3 interacts with the lysosomal calcium channel TRPML1, facilitating calcium efflux essential for TFEB activation. Furthermore, we demonstrate the presence and importance of this TFEB activation mechanism in kidneys in a mouse model of oxalate nephropathy accompanying lysosomal damage. A proximal tubule-specific TFEB-knockout mouse exhibited progression of kidney injury induced by oxalate crystals. Together, our results reveal unexpected mechanisms of TFEB activation by LC3 lipidation and their physiological relevance during the lysosomal damage response.
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FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
In this study, the interfacial strength and fracture behavior of Ag/Si interfaces formed by a composite paste comprising Ag2O microparticles, Ag microflakes, and terpineol is demonstrated through ...microscale tensile testing. This paste induces a delayed reduction of Ag2O and subsequent interconnection between the Ag grains and Si substrate. This is owing to the interface formation by the direct bonding of Ag and a layer with Ag nanoparticles intermediated bonding using the newly generated Ag nanoparticles. This characteristic interface formation helps achieve a high joint strength (>30 MPa) at a bonding temperature of 250 °C, inducing a substrate fracture at 275 °C. Microscale tensile testing reveals the high-strength Ag/Si (>200 MPa) interface formation and intrinsic fracture morphology within the Ag layer at a nanoscale; the fracture occurs in the Ag layer and not at the interface.
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GEOZS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Although erosions and ulcerations are the most common small-bowel abnormalities found on wireless capsule endoscopy (WCE), a computer-aided detection method has not been established. We aimed to ...develop an artificial intelligence system with deep learning to automatically detect erosions and ulcerations in WCE images.
We trained a deep convolutional neural network (CNN) system based on a Single Shot Multibox Detector, using 5360 WCE images of erosions and ulcerations. We assessed its performance by calculating the area under the receiver operating characteristic curve and its sensitivity, specificity, and accuracy using an independent test set of 10,440 small-bowel images including 440 images of erosions and ulcerations.
The trained CNN required 233 seconds to evaluate 10,440 test images. The area under the curve for the detection of erosions and ulcerations was 0.958 (95% confidence interval CI, 0.947-0.968). The sensitivity, specificity, and accuracy of the CNN were 88.2% (95% CI, 84.8%-91.0%), 90.9% (95% CI, 90.3%-91.4%), and 90.8% (95% CI, 90.2%-91.3%), respectively, at a cut-off value of 0.481 for the probability score.
We developed and validated a new system based on CNN to automatically detect erosions and ulcerations in WCE images. This may be a crucial step in the development of daily-use diagnostic software for WCE images to help reduce oversights and the burden on physicians.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background and Aim
Although small‐bowel angioectasia is reported as the most common cause of bleeding in patients and frequently diagnosed by capsule endoscopy (CE) in patients with obscure ...gastrointestinal bleeding, a computer‐aided detection method has not been established. We developed an artificial intelligence system with deep learning that can automatically detect small‐bowel angioectasia in CE images.
Methods
We trained a deep convolutional neural network (CNN) system based on Single Shot Multibox Detector using 2237 CE images of angioectasia. We assessed its diagnostic accuracy by calculating the area under the receiver operating characteristic curve (ROC‐AUC), sensitivity, specificity, positive predictive value, and negative predictive value using an independent test set of 10 488 small‐bowel images, including 488 images of small‐bowel angioectasia.
Results
The AUC to detect angioectasia was 0.998. Sensitivity, specificity, positive predictive value, and negative predictive value of CNN were 98.8%, 98.4%, 75.4%, and 99.9%, respectively, at a cut‐off value of 0.36 for the probability score.
Conclusions
We developed and validated a new system based on CNN to automatically detect angioectasia in CE images. This may be well applicable to daily clinical practice to reduce the burden of physicians as well as to reduce oversight.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Protruding lesions of the small bowel vary in wireless capsule endoscopy (WCE) images, and their automatic detection may be difficult. We aimed to develop and test a deep learning–based system to ...automatically detect protruding lesions of various types in WCE images.
We trained a deep convolutional neural network (CNN), using 30,584 WCE images of protruding lesions from 292 patients. We evaluated CNN performance by calculating the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity, using an independent set of 17,507 test images from 93 patients, including 7507 images of protruding lesions from 73 patients.
The developed CNN analyzed 17,507 images in 530.462 seconds. The AUC for detection of protruding lesions was 0.911 (95% confidence interval Cl, 0.9069–0.9155). The sensitivity and specificity of the CNN were 90.7% (95% CI, 90.0%–91.4%) and 79.8% (95% CI, 79.0%–80.6%), respectively, at the optimal cut-off value of 0.317 for probability score. In a subgroup analysis of the category of protruding lesions, the sensitivities were 86.5%, 92.0%, 95.8%, 77.0%, and 94.4% for the detection of polyps, nodules, epithelial tumors, submucosal tumors, and venous structures, respectively. In individual patient analyses (n = 73), the detection rate of protruding lesions was 98.6%.
We developed and tested a new computer-aided system based on a CNN to automatically detect various protruding lesions in WCE images. Patient-level analyses with larger cohorts and efforts to achieve better diagnostic performance are necessary in further studies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Memories are initially encoded in the hippocampus but subsequently consolidated to the cortex. Although synaptic plasticity is key to these processes, its precise spatiotemporal profile remains ...poorly understood. Using optogenetics to selectively erase long-term potentiation (LTP) within a defined temporal window, we found that distinct phases of synaptic plasticity play differential roles. The first wave acts locally in the hippocampus to confer context specificity. The second wave, during sleep on the same day, organizes these neurons into synchronously firing assemblies. Finally, LTP in the anterior cingulate cortex during sleep on the second day is required for further stabilization of the memory. This demonstrates the precise localization, timing, and characteristic contributions of the plasticity events that underlie the early phase of memory consolidation.
Hemostasis is an essential function that repairs tissues and maintains the survival of living organisms. To prevent diseases caused by the abnormality of the blood coagulation mechanism, it is ...important to carry out a blood test periodically by a method that is convenient and less burdensome for examiners. Thrombin is a protease that catalyzes the conversion of fibrinogen, and its cleavage activity can be an index of coagulation activity. Here, we developed a ratiometric bioluminescent indicator, Thrombastor (thrombin activity sensing indicator), which reflects the thrombin cleavage activity in blood by changing the emission color from green to blue. Compared to the current thrombin activity indicator, the rapid color change of the emission indicated a 2.5-fold decrease in the K m for thrombin, and the cleavage rate was more than two times faster. By improving the absolute bioluminescence intensity, detection from a small amount of plasma could be achieved with a smartphone camera. Using Thrombastor and a versatile device, an effective diagnosis for preventing coagulation disorders can be provided.
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IJS, KILJ, NUK, PNG, UL, UM
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•Galvannealed high strength steel and 6061 aluminum alloy was joined by friction stir spot welding.•Discharge of zinc attributed to galvannealed layer causes formation of interfacial ...microstructure including defects.•Microscale tensile testing using notched specimen enables to elucidate the fracture dominant of dissimilar joints.•Macroscale joint strength was dominated by the aluminum/reaction layer interface at the outermost region with few defects.
The macroscale mechanical properties of dissimilar joints are generally influenced by the fracture behavior of joint interface. However, little is known about the dominant factor for the joint properties related with both macroscale fracture behavior and microscale interfacial properties. Herein, microscale tensile testing of the joint interface was coupled with the macroscale fracture evaluation to elucidate the dominant factor of strength in dissimilar joints between 6061 aluminum alloy and high tensile strength galvannealed steel via friction stir spot welding (FSSW). Microstructural analyses revealed the characteristic formation of interfacial microstructure accompanied by friction and Zn discharge during the FSSW process. Microscale tensile testing was performed on the specimen on which the pre-notch was introduced to induce local fracture at the intended position on the joint interface. Results showed the presence of the weakest interface attributed to initial joining defects formed by Zn concentration at the outer area, which were consistent with the outside of the crack arresting area confirmed by macroscale evaluation. These results indicated that the joint strength of dissimilar joints between 6061 aluminum alloy and galvannealed steel is dominated by the local strength of the joining area without defects and suggested a process design for improving dissimilar joints.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background and Aim
To examine whether our convolutional neural network (CNN) system based on deep learning can reduce the reading time of endoscopists without oversight of abnormalities in the ...capsule‐endoscopy reading process.
Methods
Twenty videos of the entire small‐bowel capsule endoscopy procedure were prepared, each of which included 0–5 lesions of small‐bowel mucosal breaks (erosions or ulcerations). At another institute, two reading processes were compared: (A) endoscopist‐alone readings and (B) endoscopist readings after the first screening by the proposed CNN. In process B, endoscopists read only images detected by CNN. Two experts and four trainees independently read 20 videos each (10 for process A and 10 for process B). Outcomes were reading time and detection rate of mucosal breaks by endoscopists. Gold standard was findings at the original institute by two experts.
Results
Mean reading time of small‐bowel sections by endoscopists was significantly shorter during process B (expert, 3.1 min; trainee, 5.2 min) compared to process A (expert, 12.2 min; trainee, 20.7 min) (P < 0.001). For 37 mucosal breaks, detection rate by endoscopists did not significantly decrease in process B (expert, 87%; trainee, 55%) compared to process A (expert, 84%; trainee, 47%). Experts detected all eight large lesions (>5 mm), but trainees could not, even when supported by the CNN.
Conclusions
Our CNN‐based system for capsule endoscopy videos reduced the reading time of endoscopists without decreasing the detection rate of mucosal breaks. However, the reading level of endoscopists should be considered when using the system.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
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Joining of 5083 and 6063 aluminum alloys to 304 stainless steel was successfully achieved by high-frequency linear friction welding working at 245 Hz with varied friction pressure and ...time, which affect the heat input. Increasing the friction pressure and friction time resulted in the softening of aluminum alloys, which facilitated plastic flow and subsequent squeezing behavior. The morphology of the intermetallic compound layer, dependent on the plastic flow, determined the performance of 5083 aluminum alloy/steel joints. Excessive friction pressure and time led to inefficient welding in 6063 aluminum alloy/steel joints because the softening and squeezing behavior of the heat-treatable alloy was susceptible to the heat input. Highly efficient joints were obtained in a short duration, i.e., 1 s, through the formation of a thin intermetallic compound layer at the interface below 500 and 50 nm for 5083 and 6063 aluminum alloy/steel joints by controlling the appropriate friction pressure. High-frequency linear friction welding was demonstrated to be effective for the sound joining of various materials by controlling the friction pressure.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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