The electrical repair of device circuits has been considered a main issue in the area of electronic packaging. Demand for self‐healing conductors as cost‐effective and promising materials for ...prolonging the durability of devices has increased. Recently, diverse designs of self‐healing and deformable circuits have been introduced in virtue of their high stretchability and conductivity. However, encapsulating a liquid metal with a polymer in a micro‐size container is essential for real applications. In this work, core–shell‐structured liquid metal microcapsules (LMCs, diameter = 2–10 µm) are synthesized via in situ polymerization of urea‐formaldehyde onto liquid metal colloids. Passivation films comprising LMC/polymer composites are simply prepared using phase separation between the capsules and the liquid prepolymer. Capsules ruptured by cutting or pressing release and transport liquid metal to the damaged sites, leading to effective recovery of electrical pathways. Such self‐healing of the metal contacts shows the high potential of LMCs for smart passivation of electronic devices. As an example, flexible perovskite solar cells incorporated with the passivation film demonstrate perfect recovery of the photovoltaic parameters immediately after cutting the metal contact, exhibiting a power conversion efficiency (PCE) retention of 99% relative to the initial value (PCE = 15.07%).
Liquid metal microcapsules (LMCs) are prepared by in situ polymerization of urea‐formaldehyde. A flexible perovskite solar cell employing the passivation film made of LMCs exhibits an excellent recovery rate from mechanical damage, 99% of initial power conversion efficiencies.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Tumor-infiltrating lymphocytes (TILs) have been known for their strong prognostic and predictive significance in triple-negative breast cancer (TNBC). Several mechanisms for TIL influx in TNBC have ...been elucidated. Major histocompatibility complex class II (MHC-II) is an essential component of the adaptive immune system and is generally restricted to the surface of antigen-presenting cells. However, it has been reported that interferon-gamma signaling may induce MHC-II in almost all cell types, including those derived from cancer. We aimed to examine the relationship between MHC-II expression in tumor cells and the amount of TILs in 681 patients with TNBC. Further, the prognostic significance of MHC-II and the association of MHC-II with a couple of molecules involved in the interferon signaling pathway were investigated using immunohistochemical staining. Higher MHC-II expression in tumor cells was associated with the absence of lymphovascular invasion (p = 0.042); larger amounts of TILs (p < 0.001); frequent formations of tertiary lymphoid structures (p < 0.001); higher expression of myxovirus resistance gene A, one of the main mediators of the interferon signaling pathway (p < 0.001); and higher expression of double-stranded RNA-activated protein kinase, which can be induced by interferons (p = 0.008). Moreover, tumors that showed high MHC class I expression and any positivity for MHC-II had larger amounts of CD4- and CD8-positive T lymphocytes (p < 0.001). Positive MHC-II expression in tumor cells was associated with better disease-free survival in patients who had lymph node metastasis (p = 0.009). In conclusion, MHC-II expression in tumor cells was closely associated with an increase in TIL number and interferon signaling in TNBC. Further studies are warranted to improve our understanding regarding TIL influx, as well as patients' responses to immunotherapy.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Here, we demonstrate a role for the mitochondrial NAD-dependent deacetylase Sirt3 in the maintenance of basal ATP levels and as a regulator of mitochondrial electron transport. We note that Sirt3⁻/⁻ ...mouse embryonic fibroblasts have a reduction in basal ATP levels. Reconstitution with wild-type but not a deacetylase-deficient form of Sirt3 restored ATP levels in these cells. Furthermore in wild-type mice, the resting level of ATP correlates with organ-specific Sirt3 protein expression. Remarkably, in mice lacking Sirt3, basal levels of ATP in the heart, kidney, and liver were reduced >50%. We further demonstrate that mitochondrial protein acetylation is markedly elevated in Sirt3⁻/⁻ tissues. In addition, in the absence of Sirt3, multiple components of Complex I of the electron transport chain demonstrate increased acetylation. Sirt3 can also physically interact with at least one of the known subunits of Complex I, the 39-kDa protein NDUFA9. Functional studies demonstrate that mitochondria from Sirt3⁻/⁻ animals display a selective inhibition of Complex I activity. Furthermore, incubation of exogenous Sirt3 with mitochondria can augment Complex I activity. These results implicate protein acetylation as an important regulator of Complex I activity and demonstrate that Sirt3 functions in vivo to regulate and maintain basal ATP levels.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Targeted next-generation sequencing (NGS) technology detects specific mutations that can provide treatment opportunities for colorectal cancer (CRC) patients. We included 145 CRC patients who ...underwent surgery. We analyzed the mutation frequencies of common actionable genes and their association with clinicopathological characteristics and oncologic outcomes using targeted NGS. Approximately 97.9% (142) of patients showed somatic mutations. Frequent mutations were observed in TP53 (70%), APC (60%), and KRAS (49%). TP53 mutations were significantly linked to higher overall stage (p = 0.038) and lower disease-free survival (DFS) (p = 0.039). ATM mutation was significantly associated with higher tumor stage (p = 0.012) and shorter overall survival (OS) (p = 0.041). Stage 3 and 4 patients with ATM mutations (p = 0.023) had shorter OS, and FBXW7 mutation was significantly associated with shorter DFS (p = 0.002). However, the OS of patients with or without TP53, RAS, APC, PIK3CA, and SMAD4 mutations did not differ significantly (p = 0.59, 0.72, 0.059, 0.25, and 0.12, respectively). Similarly, the DFS between patients with RAS, APC, PIK3CA, and SMAD4 mutations and those with wild-type were not statistically different (p = 0.3, 0.79, 0.13, and 0.59, respectively). In multivariate Cox regression analysis, ATM mutation was an independent biomarker for poor prognosis of OS (p = 0.043). A comprehensive analysis of the molecular markers for CRC can provide insights into the mechanisms underlying disease progression and help optimize a personalized therapy.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background
Pruritus is a highly burdensome symptom in patients with epidermolysis bullosa, especially recessive dystrophic epidermolysis bullosa (RDEB); however, only a few studies have assessed the ...molecular pathogenesis of RDEB‐associated pruritus. Interleukin (IL)‐31 is a key cytokine implicated in pruritus associated with dermatologic diseases such as atopic dermatitis and prurigo nodularis.
Objective
To investigate the role and cellular source of IL‐31 in RDEB‐associated pruritus.
Methods
Serum and skin samples were obtained from 11 RDEB patients and 11 healthy controls. Pruritus visual analogue scale scores were determined. Serum levels of IL‐31 and thymic stromal lymphopoietin (TSLP) were examined by enzyme‐linked immunosorbent assay (ELISA). The expression of IL‐31 and other pruritus mediators in the skin were examined through immunofluorescence staining, and their correlation with pruritus severity was analysed.
Results
Serum IL‐31 and TSLP were elevated in RDEB patients. IL‐31 expression was increased in RDEB skin and positively correlated with pruritus severity. Most of the IL‐31‐expressing cells were mast cells, and some were CD206(+) M2‐like macrophages. The number of substance P(+) cells was also increased in the patients' skin, and most of them were mast cells. The number of substance P(+) mast cells was correlated with the number of IL‐31(+) dermal infiltrates. The number of IL‐4Rα‐ and IL‐13‐expressing cells and expression of TSLP and periostin increased in RDEB skin, but without a correlation to pruritus score.
Conclusion
The increased production of skin IL‐31 from mast cells and M2‐like macrophages may be the mechanism underlying pruritus in RDEB.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
High levels of microsatellite instability (MSI‐H) occurs in about 15% of sporadic colorectal cancer (CRC) and is an important predictive marker for response to immune checkpoint inhibitors. To test ...the feasibility of a deep learning (DL)‐based classifier as a screening tool for MSI status, we built a fully automated DL‐based MSI classifier using pathology whole‐slide images (WSIs) of CRCs. On small image patches of The Cancer Genome Atlas (TCGA) CRC WSI dataset, tissue/non‐tissue, normal/tumor and MSS/MSI‐H classifiers were applied sequentially for the fully automated prediction of the MSI status. The classifiers were also tested on an independent cohort. Furthermore, to test how the expansion of the training data affects the performance of the DL‐based classifier, additional classifier trained on both TCGA and external datasets was tested. The areas under the receiver operating characteristic curves were 0.892 and 0.972 for the TCGA and external datasets, respectively, by a classifier trained on both datasets. The performance of the DL‐based classifier was much better than that of previously reported histomorphology‐based methods. We speculated that about 40% of CRC slides could be screened for MSI status without molecular testing by the DL‐based classifier. These results demonstrated that the DL‐based method has potential as a screening tool to discriminate molecular alteration in tissue slides.
What's new?
Microsatellite instability (MSI) levels are an important predictive biomarker for response to immune checkpoint inhibitors in colorectal cancer. To test the feasibility of a deep learning (DL)‐based classifier as a screening tool for MSI status, here the authors built a fully‐automated DL‐based MSI classifier using pathology whole‐slide images of hematoxylin and eosin‐stained tissue slides of colorectal cancer. By automatically removing artefacts and selecting tumour patches with high tumour probability, the DL‐based system could screen out a considerable number of tissue slides for their MSI status, demonstrating its potential as a screening tool for molecular alterations in tissue slides.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The level of tumor-infiltrating lymphocytes and presence of tertiary lymphoid structures are significant prognostic and predictive factors in primary breast cancer. However, the understanding about ...differences in tumor-infiltrating lymphocytes and tertiary lymphoid structures at various metastatic sites or between primary breast tumors and metastatic sites is limited. A total of 335 cases of metastatic breast cancer from four metastatic sites (lung, liver, brain, and ovary) were included. We analyzed the percentages of tumor-infiltrating lymphocytes and presence of tertiary lymphoid structures in the primary and metastatic sites. The mean level of tumor-infiltrating lymphocytes in the lung metastases was higher than in the liver, brain, ovary, and matched primary tumors, while metastatic tumors of the liver and brain showed lower levels of tumor-infiltrating lymphocytes than primary tumors. Tertiary lymphoid structures were only found in the lung and liver, and in cases of brain metastases the change of tertiary lymphoid structures from present to absent significantly affected the level of tumor-infiltrating lymphocytes in metastases compared with that in matched primary tumors. Patients with a lower histological grade, hormone receptor positivity in primary tumors and metastases, a lower level of tumor-infiltrating lymphocytes and absence of tertiary lymphoid structures in primary tumors, a higher level of tumor-infiltrating lymphocytes and presence of tertiary lymphoid structures in metastases, and lung metastases showed significantly better overall survival. Our results showed that metastatic breast tumors in the lung had more tumor-infiltrating lymphocytes than did tumors at other sites and matched primary tumors. In addition, the presence of tertiary lymphoid structures in metastatic sites is a critical factor for the level of tumor-infiltrating lymphocytes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Fast and accurate confirmation of metastasis on the frozen tissue section of intraoperative sentinel lymph node biopsy is an essential tool for critical surgical decisions. However, accurate ...diagnosis by pathologists is difficult within the time limitations. Training a robust and accurate deep learning model is also difficult owing to the limited number of frozen datasets with high quality labels. To overcome these issues, we validated the effectiveness of transfer learning from CAMELYON16 to improve performance of the convolutional neural network (CNN)-based classification model on our frozen dataset (N = 297) from Asan Medical Center (AMC). Among the 297 whole slide images (WSIs), 157 and 40 WSIs were used to train deep learning models with different dataset ratios at 2, 4, 8, 20, 40, and 100%. The remaining, i.e., 100 WSIs, were used to validate model performance in terms of patch- and slide-level classification. An additional 228 WSIs from Seoul National University Bundang Hospital (SNUBH) were used as an external validation. Three initial weights, i.e., scratch-based (random initialization), ImageNet-based, and CAMELYON16-based models were used to validate their effectiveness in external validation. In the patch-level classification results on the AMC dataset, CAMELYON16-based models trained with a small dataset (up to 40%, i.e., 62 WSIs) showed a significantly higher area under the curve (AUC) of 0.929 than those of the scratch- and ImageNet-based models at 0.897 and 0.919, respectively, while CAMELYON16-based and ImageNet-based models trained with 100% of the training dataset showed comparable AUCs at 0.944 and 0.943, respectively. For the external validation, CAMELYON16-based models showed higher AUCs than those of the scratch- and ImageNet-based models. Model performance for slide feasibility of the transfer learning to enhance model performance was validated in the case of frozen section datasets with limited numbers.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Diesel exhaust particulates (DEP) have adverse effects on the respiratory system. Endoplasmic reticulum (ER) abnormalities contribute to lung inflammation. However, the relationship between DEP ...exposure and ER stress in the respiratory immune system and especially the alveolar macrophages (AM) is poorly understood. Here, we examined ER stress and inflammatory responses using both in vivo and in vitro study. For in vivo study, mice were intratracheally instilled with 25, 50, and 100 μg DEP and in vitro AM were stimulated with DEP at 1, 2, and 3 mg/mL. DEP increased lung weight and the number of inflammatory cells, especially neutrophils, and inflammatory cytokines in bronchoalveolar lavage fluid of mice. DEP also increased the number of DEP-pigmented AM and ER stress markers including bound immunoglobulin protein (BiP) and CCAAT/enhancer binding protein-homologous protein (CHOP) were upregulated in the lungs of DEP-treated mice. In an in vitro study, DEP caused cell damage, increased intracellular reactive oxygen species, and upregulated inflammatory genes and ER stress-related BiP, CHOP, splicing X-box binding protein 1, and activating transcription factor 4 expressions in AM. Furthermore, DEP released the C-X-C Motif Chemokine Ligand 1 (CXCL1/KC) in AM. In conclusion, DEP may contribute to neutrophilic lung inflammation pathogenesis by modulating ER stress-mediated CXCL1/KC expression in AM.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The facial artery is the main artery supplying blood to the face and is known to have facial branches of the inferior labial, superior labial, lateral nasal and angular arteries. These known major ...branches of facial artery run medially, however, there are sometimes branches of the facial artery heading laterally. The purpose of the present study was to investigate the lateral branches of the facial artery in face. We dissected facial branches of the facial artery in 74 cadaveric hemifaces. We investigated the presence of the lateral branches of the facial artery. Following parameters were investigated: lateral branch presence, the location of its origin, and the lateral branch diameter. Among the lateral branches, we evaluated the prevalence and diameter of the premasseteric branch. Lateral branches were observed in 48 of the 74 hemifaces (64.9%). The total number was 81 in the 48 hemifaces. The most common origin was between the inferior border of the mandible and inferior labial artery origin (42 of 81, 51.9%). The mean diameter of all lateral branches of the facial artery was 0.7 mm. Among the lateral branches, the premasseteric branches were present in 38 of 74 specimen (51.4%) and the mean diameter was 0.8 mm. The lateral branches of the facial artery may be registered in Terminologia Anatomica based on their prevalence. Accurate knowledge of the anatomy of the lateral branches of the facial artery is helpful for clinicians to avoid complications during facial procedures or maxillofacial surgeries.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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