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The first enantioselective total synthesis of kopsiyunnanine B, which has a unique folded and complex pentacyclic structure containing six contiguous chiral centers, has been achieved along our originally proposed biosynthetic pathway. The key reaction of this synthesis includes a bioinspired cascade that builds three ring structures and three chiral centers in one step and features the stereoselective reduction of a ß-acrylate and oxidation to an oxindole.
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Estereoisomerismo , OxirreduçãoRESUMO
Photo-functionalization of titanium orthopedic/prosthetic implants using ultraviolet illumination is known to improve osteogenesis. Therefore, in this study, we aimed to examine the influence of vacuum ultraviolet (VUV)-treated titanium surfaces on osteoblast cell adhesion, activity, and differentiation. Osteoblastic cells were cultured on titanium substrates treated with various VUV treatment conditions (0, 6.2, 18.7, and 37.4 J/cm2) and their behavior was evaluated. The results revealed that cell adhesion was increased whereas cell activity and differentiation ability were decreased upon cell culture on VUV-treated substrates. In particular, cell activity and differentiation ability were dramatically suppressed with 18.7 J/cm2 VUV irradiation. Within the limitations of this cell-based experiment, we clarified the VUV treatment conditions in which cell adhesion was improved but cell activity and differentiation ability were suppressed. These results indicate that VUV-treatment can be used to influence cell growth properties and can be used to accelerate or suppress cell differentiation on implant substrates.
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Diferenciação Celular/efeitos da radiação , Proliferação de Células/efeitos da radiação , Osteogênese/efeitos dos fármacos , Titânio/farmacologia , Adesão Celular/efeitos dos fármacos , Adesão Celular/efeitos da radiação , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Humanos , Osteoblastos/efeitos dos fármacos , Osteoblastos/efeitos da radiação , Osteogênese/genética , Osteogênese/efeitos da radiação , Especificidade por Substrato , Propriedades de Superfície/efeitos dos fármacos , Propriedades de Superfície/efeitos da radiação , Raios Ultravioleta/efeitos adversos , VácuoRESUMO
PURPOSE: Estimating the surgery length has the potential to be utilized as skill assessment, surgical training, or efficient surgical facility utilization especially if it is done in real-time as a remaining surgery duration (RSD). Surgical length reflects a certain level of efficiency and mastery of the surgeon in a well-standardized surgery such as cataract surgery. In this paper, we design and develop a real-time RSD estimation method for cataract surgery that does not require manual labeling and is transferable with minimum fine-tuning. METHODS: A regression method consisting of convolutional neural networks (CNNs) and long short-term memory (LSTM) is designed for RSD estimation. The model is firstly trained and evaluated for the single main surgeon with a large number of surgeries. Then, the fine-tuning strategy is used to transfer the model to the data of the other two surgeons. Mean Absolute Error (MAE in seconds) was used to evaluate the performance of the RSD estimation. The proposed method is compared with the naïve method which is based on the statistic of the historical data. A transferability experiment is also set to demonstrate the generalizability of the method. RESULT: The mean surgical time for the sample videos was 318.7 s (s) (standard deviation 83.4 s) for the main surgeon for the initial training. In our experiments, the lowest MAE of 19.4 s (equal to about 6.4% of the mean surgical time) is achieved by our best-trained model for the independent test data of the main target surgeon. It reduces the MAE by 35.5 s (-10.2%) compared to the naïve method. The fine-tuning strategy transfers the model trained for the main target to the data of other surgeons with only a small number of training data (20% of the pre-training). The MAEs for the other two surgeons are 28.3 s and 30.6 s with the fine-tuning model, which decreased by -8.1 s and -7.5 s than the Per-surgeon model (average declining of -7.8 s and 1.3% of video duration). External validation study with Cataract-101 outperformed 3 reported methods of TimeLSTM, RSDNet, and CataNet. CONCLUSION: An approach to build a pre-trained model for estimating RSD estimation based on a single surgeon and then transfer to other surgeons demonstrated both low prediction error and good transferability with minimum fine-tuning videos.
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Catarata , Memória de Curto Prazo , Humanos , Redes Neurais de ComputaçãoRESUMO
Programmed death (PD)-1/PD-ligand 1 (PD-L1) antibodies have shown an intense clinical effect in some patients with PD-L1+ tumors, and their applications have rapidly expanded to various cancer types with or without the application of new companion diagnostics (CDx) with a lower cutoff value and inclusion of macrophage evaluation. However, the pathological background explaining the difference in the cutoff value remains unknown. To address this, we evaluated tissue array samples from 231 patients with lung adenocarcinoma, 186 with lung squamous cell carcinoma, and 38 with renal cell carcinoma (RCC) who were not receiving PD-1/PD-L1 antibodies to investigate the relationship between PD-L1 expression on tumor cells and CD8+ T-cell infiltration in tumor tissues. PD-L1 expression in RCC was clearly lower than that in non-small-cell lung cancer (NSCLC) tissue, whereas CD8+ T-cell infiltration was low in all cancers. We next analyzed PD-L1 expression by interferon (α, ß, and γ) and LPS stimulation in both macrophages and 41 cancer cell lines derived from various organs and histological types. The PD-L1 expression patterns were classified into three types, which differed depending on each organ or tissue type. Interestingly, NSCLC cell lines showed highly diverse PD-L1 expression patterns compared with RCC cell lines. Conversely, PD-L1 expression was stronger and more prolonged in macrophages than in typical cell lines. Here, we revealed the diversity of the PD-L1 expression patterns in tumor cells and macrophages, demonstrating the pathological and cytological significance of the transition of cutoff values in PD-L1 CDx for PD-1/PD-L1 antibody administration.
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Antígeno B7-H1/metabolismo , Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Renais , Neoplasias Renais , Neoplasias Pulmonares , Anticorpos , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/patologia , Macrófagos/metabolismo , Receptor de Morte Celular Programada 1RESUMO
Cancer metastasis accounts for most of the mortality associated with solid tumors. However, antimetastatic drugs are not available on the market. One of the important biological events leading to metastasis is the epithelial to mesenchymal transition (EMT) induced by cytokines, namely transforming growth-factor-ß (TGF-ß). Although several classes of inhibitors targeting TGF-ß and its receptor have been developed, they have shown profound clinical side effects. We focused on our synthetic compound, HPH-15, which has shown anti-fibrotic activity via the blockade of the TGF-ß Smad-dependent signaling. In this study, 10 µM of HPH-15 was found to exhibit anti-cell migration and anti-EMT activities in non-small-cell lung cancer (NSCLC) cells. Although higher concentrations are required, the anti-EMT activity of HPH-15 has also been observed in 3D-cultured NSCLC cells. A mechanistic study showed that HPH-15 inhibits downstream TGF-ß signaling. This downstream inhibition blocks the expression of cytokines such as TGF-ß, leading to the next cycle of Smad-dependent and -independent signaling. HPH-15 has AMPK-activation activity, but a relationship between AMPK activation and anti-EMT/cell migration was not observed. Taken together, HPH-15 may lead to the development of antimetastatic drugs with a new mechanism of action.
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Carcinoma Pulmonar de Células não Pequenas , Transição Epitelial-Mesenquimal , Transdução de Sinais , Fator de Crescimento Transformador beta , Proteínas Quinases Ativadas por AMP , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta/antagonistas & inibidores , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Fatores de Crescimento TransformadoresRESUMO
A simple methylenedioxy dibromoindole alkaloid, amakusamine (1), was isolated from a marine sponge of the genus Psammocinia, and its structure was determined from spectroscopic data, time-dependent density-functional theory calculations, and synthesis. Compound 1 inhibited the receptor activator of nuclear factor-κB ligand (RANKL)-induced formation of multinuclear osteoclasts with an IC50 value of 10.5 µM in RAW264 cells. The structure-activity relationship of 1 was also investigated with synthetic derivatives.
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Alcaloides/farmacologia , Osteoclastos/efeitos dos fármacos , Poríferos/química , Ligante RANK/antagonistas & inibidores , Animais , Japão , Camundongos , Estrutura Molecular , Células RAW 264.7 , Relação Estrutura-AtividadeRESUMO
PURPOSE: The aims of this study were to evaluate the safety, efficacy, and pharmacokinetics of repeated doses of palonosetron 0.75 mg on days 1 and 3 in Japanese patients who received highly or moderately emetogenic chemotherapy. METHODS: Twenty- six patients received palonosetron 0.75 mg intravenously before chemotherapy on days 1 and 3 plus dexamethasone (12-16 mg before chemotherapy on day 1 and 4-8 mg on days 2 and 3). The primary endpoints were safety and pharmacokinetics. Pharmacokinetics were evaluated in a subset of patients (n=6). Complete response and complete protection were evaluated as secondary endpoints. RESULTS: The accumulation ratios for C max and AUClast after the second dose on day 3 were 1.42 and 1.37, respectively. These values were consistent with the theoretical values expected from the half-life of palonosetron on day 1. Almost all of the patients had no nausea or vomiting in the acute phase (complete response (CR) rate, 96.2% [25/26]; CP rate, 92.3% [24/26]). In the delayed phase (24-192 h post-chemotherapy), the complete response and complete protection rates were 76.9% (20/26) and 61.5% (16/26), respectively. Treatment was well tolerated. CONCLUSIONS: This is the first study to report the pharmacokinetics of multiple doses of palonosetron 0.75 mg, given on days 1 and 3, in Japanese patients. Repeated treatment with palonosetron was safe and well tolerated by patients who received highly or moderately emetogenic anticancer chemotherapy.
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Antieméticos/efeitos adversos , Antieméticos/farmacocinética , Isoquinolinas/efeitos adversos , Isoquinolinas/farmacocinética , Neoplasias/metabolismo , Quinuclidinas/efeitos adversos , Quinuclidinas/farmacocinética , Antagonistas da Serotonina/efeitos adversos , Antagonistas da Serotonina/farmacocinética , Adulto , Idoso , Antieméticos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Dexametasona/uso terapêutico , Feminino , Humanos , Injeções Intravenosas , Isoquinolinas/administração & dosagem , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Náusea/metabolismo , Náusea/prevenção & controle , Neoplasias/tratamento farmacológico , Palonossetrom , Quinuclidinas/administração & dosagem , Antagonistas da Serotonina/administração & dosagem , Vômito/induzido quimicamente , Vômito/metabolismo , Vômito/prevenção & controleRESUMO
The content-style duality is a fundamental element in art. These two dimensions can be easily differentiated by humans: content refers to the objects and concepts in an artwork, and style to the way it looks. Yet, we have not found a way to fully capture this duality with visual representations. While style transfer captures the visual appearance of a single artwork, it fails to generalize to larger sets. Similarly, supervised classification-based methods are impractical since the perception of style lies on a spectrum and not on categorical labels. We thus present GOYA, which captures the artistic knowledge of a cutting-edge generative model for disentangling content and style in art. Experiments show that GOYA explicitly learns to represent the two artistic dimensions (content and style) of the original artistic image, paving the way for leveraging generative models in art analysis.
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We introduce an emotional stimuli detection task that targets extracting emotional regions that evoke people's emotions (i.e., emotional stimuli) in artworks. This task offers new challenges to the community because of the diversity of artwork styles and the subjectivity of emotions, which can be a suitable testbed for benchmarking the capability of the current neural networks to deal with human emotion. For this task, we construct a dataset called APOLO for quantifying emotional stimuli detection performance in artworks by crowd-sourcing pixel-level annotation of emotional stimuli. APOLO contains 6781 emotional stimuli in 4718 artworks for validation and testing. We also evaluate eight baseline methods, including a dedicated one, to show the difficulties of the task and the limitations of the current techniques through qualitative and quantitative experiments.
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Living cells are constantly subjected to various mechanical stimulations, such as shear flow, osmotic pressure, and hardness of substratum. They must sense the mechanical aspects of their environment and respond appropriately for proper cell function. Cells adhering to substrata must receive and respond to mechanical stimuli from the substrata to decide their shape and/or migrating direction. In response to cyclic stretching of the elastic substratum, intracellular stress fibers in fibroblasts and endothelial, osteosarcoma, and smooth muscle cells are rearranged perpendicular to the stretching direction, and the shape of those cells becomes extended in this new direction. In the case of migrating Dictyostelium cells, cyclic stretching regulates the direction of migration, and not the shape, of the cell. The cells migrate in a direction perpendicular to that of the stretching. However, the molecular mechanisms that induce the directional migration remain unknown. Here, using a microstretching device, we recorded green fluorescent protein (GFP)-myosin-II dynamics in Dictyostelium cells on an elastic substratum under cyclic stretching. Repeated stretching induced myosin II localization equally on both stretching sides in the cells. Although myosin-II-null cells migrated randomly, myosin-II-null cells expressing a variant of myosin II that cannot hydrolyze ATP migrated perpendicular to the stretching. These results indicate that Dictyostelium cells accumulate myosin II at the portion of the cell where a large strain is received and migrate in a direction other than that of the portion where myosin II accumulated. This polarity generation for migration does not require the contraction of actomyosin.
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Movimento Celular , Corrente Citoplasmática , Miosina Tipo II/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Dictyostelium/citologia , Dictyostelium/genética , Dictyostelium/metabolismo , Dictyostelium/fisiologia , Proteínas de Fluorescência Verde/genética , Hidrólise , Mutação , Miosina Tipo II/genética , Pseudópodes/metabolismo , Pseudópodes/ultraestrutura , Estresse MecânicoRESUMO
The first asymmetric total synthesis of the Lycopodium alkaloid senepodine F, which contains a decahydroquinoline ring (AB-ring) and a quinolizidine ring (CD-ring) connected by a methylene tether, has been achieved. The key steps of this synthesis include an organocatalytic asymmetric Diels-Alder reaction, a diastereoselective intramolecular aza-Michael reaction, and an intramolecular SN2 cyclization to construct multisubstituted nitrogen-containing heterocycles. In addition, our total synthesis led to the stereochemical reassignment on the decahydroquinoline ring of senepodine F.
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The morphological feature of retinal arterio-venous crossing patterns is a valuable source of cardiovascular risk stratification as it directly captures vascular health. Although Scheie's classification, which was proposed in 1953, has been used to grade the severity of arteriolosclerosis as diagnostic criteria, it is not widely used in clinical settings as mastering this grading is challenging as it requires vast experience. In this paper, we propose a deep learning approach to replicate a diagnostic process of ophthalmologists while providing a checkpoint to secure explainability to understand the grading process. The proposed pipeline is three-fold to replicate a diagnostic process of ophthalmologists. First, we adopt segmentation and classification models to automatically obtain vessels in a retinal image with the corresponding artery/vein labels and find candidate arterio-venous crossing points. Second, we use a classification model to validate the true crossing point. At last, the grade of severity for the vessel crossings is classified. To better address the problem of label ambiguity and imbalanced label distribution, we propose a new model, named multi-diagnosis team network (MDTNet), in which the sub-models with different structures or different loss functions provide different decisions. MDTNet unifies these diverse theories to give the final decision with high accuracy. Our automated grading pipeline was able to validate crossing points with precision and recall of 96.3% and 96.3%, respectively. Among correctly detected crossing points, the kappa value for the agreement between the grading by a retina specialist and the estimated score was 0.85, with an accuracy of 0.92. The numerical results demonstrate that our method can achieve a good performance in both arterio-venous crossing validation and severity grading tasks following the diagnostic process of ophthalmologists. By the proposed models, we could build a pipeline reproducing ophthalmologists' diagnostic process without requiring subjective feature extractions. The code is available (https://github.com/conscienceli/MDTNet).
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L-asparaginase (L-Asp) is a useful antileukemic agent for acute lymphoblastic leukemia (ALL); however, it often causes severe liver injury with marked fatty liver. Here, we present a case of L-Asp-induced fatty liver disease in a 21-year-old female patient with ALL. Serum cholinesterase levels, which are usually elevated in fatty liver, decrease at the onset of liver injury. After treatment with L-carnitine and vitamin B complex, the liver injury rapidly improved, resulting in the patient being able to continue subsequent chemotherapy.
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AIMS: Mismatch-repair deficiency and microsatellite instability-high (dMMR/MSI-H) colorectal cancer (CRC) is treated with programmed death (PD)-1 antibody regardless of PD-ligand (L)1 expression in tumor cells. We previously found that abundant CD169+ macrophages in regional lymph node (RLN) sinuses and CD8+ tumor-infiltrating lymphocytes (TILs) positively correlated in CRC and were associated with a favorable prognosis. However, associations between dMMR/MSI-H CRC and CD8+ TILs or prognoses vary among studies. In this study, we attempted to compare the association between MMR status, CD169+ macrophages in RLNs, CD8+ TILs, PD-L1 scores, and prognoses in CRC. METHODS AND RESULTS: We immunostained 83 surgically resected CRC tumors that we previously analyzed for MMR proteins, and identified 9 that were dMMR. The number of CD169+ macrophages in RLNs and CD8+ TILs significantly correlated with overall survival, whereas MMR status did not. The number of cells positive for the TIL markers CD3, CD4, CD8, and TIA-1, and macrophage markers CD68 and CD169 in RLNs did not significantly differ between groups according to MMR status. Furthermore, combined positive scores (CPS) for PD-L1 expression in five of nine dMMR CRCs were all <1. We found that dMMR in CRC did not correlate with numbers of CD169+ macrophages in RLNs or CD8+ TILs. CONCLUSIONS: CRC with CD169+ macrophages in RLNs and abundant CD8+ TILs indicates a better prognosis and it should be immunologically classified as a different antitumor group from dMMR CRC.
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Neoplasias do Colo , Neoplasias Colorretais , Humanos , Antígeno B7-H1/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/cirurgia , Prognóstico , Neoplasias do Colo/metabolismo , Linfócitos do Interstício Tumoral/patologia , Linfonodos/patologia , Macrófagos , Reparo de Erro de Pareamento de DNARESUMO
BACKGROUND: This work aims to develop a deep learning model, assessing atlantoaxial subluxation (AAS) in rheumatoid arthritis (RA), which can often be ambiguous in clinical practice. METHODS: We collected 4691 X-ray images of the cervical spine of the 906 patients with RA. Among these images, 3480 were used for training the deep learning model, 803 were used for validating the model during the training process, and the remaining 408 were used for testing the performance of the trained model. The two-dimensional key points' detection model of Deep High-Resolution Representation Learning for Human Pose Estimation was adopted as the base convolutional neural network model. The model inferred four coordinates to calculate the atlantodental interval (ADI) and space available for the spinal cord (SAC). Finally, these values were compared with those by clinicians to evaluate the performance of the model. RESULTS: Among the 408 cervical images for testing the performance, the trained model correctly identified the four coordinates in 99.5% of the dataset. The values of ADI and SAC were positively correlated among the model and two clinicians. The sensitivity of AAS diagnosis with ADI or SAC by the model was 0.86 and 0.97 respectively. The specificity of that was 0.57 and 0.5 respectively. CONCLUSIONS: We present the development of a deep learning model for the evaluation of cervical lesions of patients with RA. The model was demonstrably shown to be useful for quantitative evaluation.
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Artrite Reumatoide , Aprendizado Profundo , Humanos , Artrite Reumatoide/complicações , Artrite Reumatoide/diagnóstico por imagem , Vértebras Cervicais , Redes Neurais de ComputaçãoRESUMO
Conventional 3D convolutional neural networks (CNNs) are computationally expensive, memory intensive, prone to overfitting, and most importantly, there is a need to improve their feature learning capabilities. To address these issues, we propose spatio-temporal short-term Fourier transform (STFT) blocks, a new class of convolutional blocks that can serve as an alternative to the 3D convolutional layer and its variants in 3D CNNs. An STFT block consists of non-trainable convolution layers that capture spatially and/or temporally local Fourier information using an STFT kernel at multiple low frequency points, followed by a set of trainable linear weights for learning channel correlations. The STFT blocks significantly reduce the space-time complexity in 3D CNNs. In general, they use 3.5 to 4.5 times less parameters and 1.5 to 1.8 times less computational costs when compared to the state-of-the-art methods. Furthermore, their feature learning capabilities are significantly better than the conventional 3D convolutional layer and its variants. Our extensive evaluation on seven action recognition datasets, including Something 2 v1 and v2, Jester, Diving-48, Kinetics-400, UCF 101, and HMDB 51, demonstrate that STFT blocks based 3D CNNs achieve on par or even better performance compared to the state-of-the-art methods.
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Algoritmos , Reconhecimento Automatizado de Padrão , Análise de Fourier , Atividades Humanas , Humanos , Redes Neurais de ComputaçãoRESUMO
Fluid control on a paper channel is necessary for analysis with multiple reagents, such as enzyme-linked immunosorbent assay (ELISA) in microfluidic paper-based analytical devices (µPADs). In this study, a thermo-responsive valve was fabricated by polymerizing N-isopropylacrylamide on a PVDF porous membrane by plasma-induced graft polymerization. The polymerized membrane was observed by scanning electron microscopy (SEM), and it was confirmed that more pores were closed at temperatures below 32 °C and more pores were opened at temperatures above 32 °C. Valve permeability tests confirmed that the proposed polymerized membrane was impermeable to water and proteins at temperatures below 32 °C and permeable to water at temperatures above 32 °C. The valve could also be reversibly and repeatedly opened and closed by changing the temperature near 32 °C. These results suggest that plasma-induced graft polymerization may be used to produce thermo-responsive valves that can be opened and closed without subsequent loss of performance. These results indicate that the thermo-responsive valve fabricated by plasma-induced graft polymerization could potentially be applied to ELISA with µPADs.
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It is difficult to fabricate three-dimensional structures using semiconductor-process technology, because it is based on two-dimensional layered structure fabrication and the etching of thin films. In this study, we fabricated metal structures that can be dynamically deformed from two-dimensional to three-dimensional shapes by combining patterning using photolithography with electroforming technology. First, a resist structure was formed on a Cu substrate. Then, using a Ni sulfamate electroforming bath, a Ni structure was formed by electroforming the fabricated resist structure. Finally, the resist structure was removed to release the Ni structure fabricated on the substrate, and electroforming was used to Au-plate the entire surface. Scanning-electron microscopy revealed that the structure presented a high aspect ratio (thickness/resist width = 3.5), and metal structures could be fabricated without defects across the entire surface, including a high aspect ratio. The metallic structures had an average film thickness of 12.9 µm with σ = 0.49 µm, hardness of 600 HV, and slit width of 7.9 µm with σ = 0.25 µm. This microfabrication enables the fabrication of metal structures that deform dynamically in response to hydrodynamic forces in liquid and can be applied to fields such as environmental science, agriculture, and medicine.
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Cancer cell count in the blood of cancer patients is extremely low. If these cells are easily detectable, cancer diagnosis may be possible by simply using a blood test, thus reducing patient burden. This study aimed to develop a cancer detection device by combining a microfilter that can be dynamically deformed and a nucleic acid aptamer that has a specific binding ability to cancer cells for easy detection. The cancer detection device was fabricated by photolithography, electroforming, and three-dimensional printing. The cancer cell detection ability of the fabricated device was evaluated using 1 mL of blood samples spiked with different concentrations of cancer cells. The lowest concentration of cancer cells in the blood was 5 cancer cells/1 mL blood. The fabricated microfilters specifically detected cancer cells in the blood successfully at exceedingly low concentrations. Moreover, the cancer detection experiment results using human whole blood revealed that cancer detection could be performed with higher accuracy using the fabricated cancer detection device compared to pre-existing cancer detection equipment (e.g., CellSearch system, Veridex). These findings provide important insights into the use of cancer cells in the blood as a diagnostic approach for cancer.
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Células Neoplásicas Circulantes , Ácidos Nucleicos , Contagem de Células , Linhagem Celular Tumoral , Separação Celular , HumanosRESUMO
Climate change is one of the most important issues for humanity. To defuse this problem, it is considered necessary to improve energy efficiency, make energy sources cleaner, and reduce energy consumption in urban areas. The Japanese government has recommended an air conditioner setting of 28°C in summer and 20°C in winter since 2005. The aim of this setting is to save energy by keeping room temperatures constant. However, it is unclear whether this is an appropriate temperature for workers and students. This study examined whether thermal environments influence task performance over time. To examine whether the relationship between task performance and thermal environments influences the psychological states of participants, we recorded their subjective rating of mental workload along with their working memory score, electroencephalogram (EEG), heart rate variability, skin conductance level (SCL), and tympanum temperature during the task and compared the results among different conditions. In this experiment, participants were asked to read some texts and answer questions related to those texts. Room temperature (18, 22, 25, or 29°C) and humidity (50%) were manipulated during the task and participants performed the task at these temperatures. The results of this study showed that the temporal cost of task and theta power of EEG, which is an index for concentration, decreased over time. However, subjective mental workload increased with time. Moreover, the low frequency to high frequency ratio and SCL increased with time and heat (25 and 29°C). These results suggest that mental workload, especially implicit mental workload, increases in warmer environments, even if learning efficiency is facilitated. This study indicates integrated evidence for relationships among task performance, psychological state, and thermal environment by analyzing behavioral, subjective, and physiological indexes multidirectionally.