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Purpose To assess the prognostic value of a deep learning-based chest radiographic age (hereafter, CXR-Age) model in a large external test cohort of Asian individuals. Materials and Methods This single-center, retrospective study included chest radiographs from consecutive, asymptomatic Asian individuals aged 50-80 years who underwent health checkups between January 2004 and June 2018. This study performed a dedicated external test of a previously developed CXR-Age model, which predicts an age adjusted based on the risk of all-cause mortality. Adjusted hazard ratios (HRs) of CXR-Age for all-cause, cardiovascular, lung cancer, and respiratory disease mortality were assessed using multivariable Cox or Fine-Gray models, and their added values were evaluated by likelihood ratio tests. Results A total of 36 924 individuals (mean chronological age, 58 years ± 7 [SD]; CXR-Age, 60 years ± 5; 22 352 male) were included. During a median follow-up of 11.0 years, 1250 individuals (3.4%) died, including 153 cardiovascular (0.4%), 166 lung cancer (0.4%), and 98 respiratory (0.3%) deaths. CXR-Age was a significant risk factor for all-cause (adjusted HR at chronological age of 50 years, 1.03; at 60 years, 1.05; at 70 years, 1.07), cardiovascular (adjusted HR, 1.11), lung cancer (adjusted HR for individuals who formerly smoked, 1.12; for those who currently smoke, 1.05), and respiratory disease (adjusted HR, 1.12) mortality (P < .05 for all). The likelihood ratio test demonstrated added prognostic value of CXR-Age to clinical factors, including chronological age for all outcomes (P < .001 for all). Conclusion Deep learning-based chest radiographic age was associated with various survival outcomes and had added value to clinical factors in asymptomatic Asian individuals, suggesting its generalizability. Keywords: Conventional Radiography, Thorax, Heart, Lung, Mediastinum, Outcomes Analysis, Quantification, Prognosis, Convolutional Neural Network (CNN) Supplemental material is available for this article. © RSNA, 2024 See also the commentary by Adams and Bressem in this issue.
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Aprendizado Profundo , Radiografia Torácica , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Feminino , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Prognóstico , Fatores de Risco , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/mortalidade , EnvelhecimentoRESUMO
Genetic code expansion involves introducing non-canonical amino acids (ncAAs) with unique functional groups into proteins to broaden their applications. Orthogonal aminoacyl tRNA synthetase (aaRS), essential for genetic code expansion, facilitates the charging of ncAAs to tRNA. In this study, we developed a new aaRS mutant from Methanosaeta concilii tyrosyl-tRNA synthetase (Mc TyrRS) to incorporate para-azido-L-phenylalanine (AzF). The development involved initial site-specific mutations in Mc TyrRS, followed by random mutagenesis. The new aaRS mutant with amber suppression was isolated through fluorescence-activated cell sorting. The M. concilii aaRS mutant structure was further analyzed to interpret the effect of mutations. This research provides a novel orthogonal aaRS evolution pipeline for highly efficient ncAA incorporation that will contribute to developing novel aaRS from various organisms.
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This study aimed to investigate the potential of beef peptides (BPs) in mitigating muscle atrophy induced by dexamethasone (DEX) with underlying three mechanisms in vitro (protein degradation, protein synthesis, and the oxidative stress pathway). Finally, the anti-atrophic effect of BPs was enhanced through purification and isolation. BPs were generated using beef loin hydrolyzed with alcalase/ProteAX/trypsin, each at a concentration of 0.67%, followed by ultrafiltration through a 3 kDa cut-off. BPs (10-100 µg mL-1) dose-dependently counteracted the DEX-induced reductions in myotube diameters, differentiation, fusion, and maturation indices (p < 0.05). Additionally, BPs significantly reduced FoxO1 protein dephosphorylation, thereby suppressing muscle-specific E3 ubiquitin ligases such as muscle RING-finger containing protein-1 and muscle atrophy F-box protein in C2C12 myotubes at concentrations exceeding 25 µg mL-1 (p < 0.05). BPs also enhanced the phosphorylation of protein synthesis markers, including mTOR, 4E-BP1, and p70S6K1, in a dose-dependent manner (p < 0.05) and increased the mRNA expression of antioxidant enzymes. Fractionated peptides derived from BPs, through size exclusion and polarity-based fractionation, also demonstrated enhanced anti-atrophic effects compared to BPs. These peptides downregulated the mRNA expression of primary muscle atrophy markers while upregulated that of antioxidant enzymes. Specifically, peptides GAGAAGAPAGGA (MW 924.5) and AFRSSTKK (MW 826.4) were identified from fractionated peptides of BPs. These findings suggest that BPs, specifically the peptide fractions GAGAAGAPAGGA and AFRSSTKK, could be a potential strategy to mitigate glucocorticoid-induced skeletal muscle atrophy by reducing the E3 ubiquitin ligase activity.
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Fibras Musculares Esqueléticas , Atrofia Muscular , Estresse Oxidativo , Peptídeos , Animais , Atrofia Muscular/tratamento farmacológico , Atrofia Muscular/metabolismo , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares Esqueléticas/metabolismo , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Peptídeos/farmacologia , Bovinos , Proteólise/efeitos dos fármacos , Linhagem Celular , Biossíntese de Proteínas/efeitos dos fármacos , Carne Vermelha , Proteínas Musculares/metabolismo , Dexametasona/farmacologia , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Fosforilação , Serina-Treonina Quinases TOR/metabolismoRESUMO
Objective.The mean squared error (MSE), also known asL2loss, has been widely used as a loss function to optimize image denoising models due to its strong performance as a mean estimator of the Gaussian noise model. Recently, various low-dose computed tomography (LDCT) image denoising methods using deep learning combined with the MSE loss have been developed; however, this approach has been observed to suffer from the regression-to-the-mean problem, leading to over-smoothed edges and degradation of texture in the image.Approach.To overcome this issue, we propose a stochastic function in the loss function to improve the texture of the denoised CT images, rather than relying on complicated networks or feature space losses. The proposed loss function includes the MSE loss to learn the mean distribution and the Pearson divergence loss to learn feature textures. Specifically, the Pearson divergence loss is computed in an image space to measure the distance between two intensity measures of denoised low-dose and normal-dose CT images. The evaluation of the proposed model employs a novel approach of multi-metric quantitative analysis utilizing relative texture feature distance.Results.Our experimental results show that the proposed Pearson divergence loss leads to a significant improvement in texture compared to the conventional MSE loss and generative adversarial network (GAN), both qualitatively and quantitatively.Significance.Achieving consistent texture preservation in LDCT is a challenge in conventional GAN-type methods due to adversarial aspects aimed at minimizing noise while preserving texture. By incorporating the Pearson regularizer in the loss function, we can easily achieve a balance between two conflicting properties. Consistent high-quality CT images can significantly help clinicians in diagnoses and supporting researchers in the development of AI-diagnostic models.
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Processamento de Imagem Assistida por Computador , Doses de Radiação , Razão Sinal-Ruído , Tomografia Computadorizada por Raios X , Tomografia Computadorizada por Raios X/métodos , Processamento de Imagem Assistida por Computador/métodos , Humanos , Aprendizado ProfundoRESUMO
Physical fitness (PF) includes various factors that significantly impacts athletic performance. Analyzing PF is critical in developing customized training methods for athletes based on the sports in which they compete. Previous approaches to analyzing PF have relied on statistical or machine learning algorithms that focus on predicting athlete injury or performance. In this study, six machine learning algorithms were used to analyze the PF of 1,489 male adolescent athletes across five sports, including track & field, football, baseball, swimming, and badminton. Furthermore, the machine learning models were utilized to analyze the essential elements of PF using feature importance of XGBoost, and SHAP values. As a result, XGBoost represents the highest performance, with an average accuracy of 90.14, an area under the curve of 0.86, and F1-score of 0.87, demonstrating the similarity between the sports. Feature importance of XGBoost, and SHAP value provided a quantitative assessment of the relative importance of PF in sports by comparing two sports within each of the five sports. This analysis is expected to be useful in analyzing the essential PF elements of athletes in various sports and recommending personalized exercise methods accordingly.
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Traumatismos em Atletas , Futebol Americano , Humanos , Masculino , Adolescente , Atletas , Futebol Americano/lesões , Natação , Aptidão FísicaRESUMO
Lairage, a part of the animal welfare practices, has been known to mitigate pre-slaughter stress in animals. However, research investigating the relationship between lairage and pork meat quality remains scarce. In this study, we conducted a comparative analysis of the physicochemical quality and storage stability of pork from pigs subjected to immediate slaughter (CON) and those provided with a 24 h lairage before slaughter (LRG) over a 7-day storage period. The loins from 20 castrated pigs in each group, respectively, were collected at 1, 3, 5, and 7 days and used for analysis of meat quality and storage stability, including pH, meat color, moisture, water holding capacity, drip loss, cooking loss, shear force, fatty acid composition, lipid oxidation, antioxidant activity, and electrical resistance. Overall, there were no significant differences in physicochemical meat quality parameters between CON and LRG groups. Similarly, no differences were observed in the storage stability of pork including 2-thiobarbituric acid reactive substances, 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity and electrical resistance. However, the proportion of unsaturated fatty acids was significantly higher in LRG compared to CON. In conclusion, 24 h lairage for castrated pigs had limited impact on meat quality and storage stability but led to an increase in the unsaturated fatty acid proportion.
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Importance: Consumer-level sleep analysis technologies have the potential to revolutionize the screening for obstructive sleep apnea (OSA). However, assessment of OSA prediction models based on in-home recording data is usually performed concurrently with level 1 in-laboratory polysomnography (PSG). Establishing the predictability of OSA using sound data recorded from smartphones based on level 2 PSG at home is important. Objective: To validate the performance of a prediction model for OSA using breathing sound recorded from smartphones in conjunction with level 2 PSG at home. Design, Setting, and Participants: This diagnostic study followed a prospective design, involving participants who underwent unattended level 2 home PSG. Breathing sounds were recorded during sleep using 2 smartphones, one with an iOS operating system and the other with an Android operating system, simultaneously with home PSG in participants' own home environment. Participants were 19 years and older, slept alone, and had either been diagnosed with OSA or had no previous diagnosis. The study was performed between February 2022 and February 2023. Main Outcomes and Measures: Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the predictive model based on the recorded breathing sounds. Results: Of the 101 participants included during the study duration, the mean (SD) age was 48.3 (14.9) years, and 51 (50.5%) were female. For the iOS smartphone, the sensitivity values at apnea-hypopnea index (AHI) levels of 5, 15, and 30 per hour were 92.6%, 90.9%, and 93.3%, respectively, with specificities of 84.3%, 94.4%, and 94.4%, respectively. Similarly, for the Android smartphone, the sensitivity values at AHI levels of 5, 15, and 30 per hour were 92.2%, 90.0%, and 92.9%, respectively, with specificities of 84.0%, 94.4%, and 94.3%, respectively. The accuracy for the iOS smartphone was 88.6%, 93.3%, and 94.3%, respectively, and for the Android smartphone was 88.1%, 93.1%, and 94.1% at AHI levels of 5, 15, and 30 per hour, respectively. Conclusions and Relevance: This diagnostic study demonstrated the feasibility of predicting OSA with a reasonable level of accuracy using breathing sounds obtained by smartphones during sleep at home.
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Apneia Obstrutiva do Sono , Smartphone , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Polissonografia , Sons Respiratórios , Apneia Obstrutiva do Sono/diagnóstico , SonoRESUMO
Concanavalin A (ConA) has an intrinsic binding affinity to carbohydrates. Here, we obtained Co2+-Ca2+-ConA (2.83 Å, PDB: 8I7Q) via X-ray crystallography by substituting native ConA (Mn2+-Ca2+); it has binding selectivity for high-mannose N-glycan similar to native ConA. Our findings may thus inform antiviral reagent design.
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Manose , Polissacarídeos , Concanavalina A/química , Polissacarídeos/química , Carboidratos , Cristalografia por Raios XRESUMO
Establishing appropriate trust and maintaining a balanced reliance on digital resources are vital for accurate optical diagnoses and effective integration of computer-aided diagnosis (CADx) in colonoscopy. Active learning using diverse polyp image datasets can help in developing precise CADx systems. Enhancing doctors' digital literacy and interpreting their results is crucial. Explainable artificial intelligence (AI) addresses opacity, and textual descriptions, along with AI-generated content, deepen the interpretability of AI-based findings by doctors. AI conveying uncertainties and decision confidence aids doctors' acceptance of results. Optimal AI-doctor collaboration requires improving algorithm performance, transparency, addressing uncertainties, and enhancing doctors' optical diagnostic skills.
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Inteligência Artificial , Colonoscopia , Diagnóstico por Computador , Humanos , Colonoscopia/métodos , Diagnóstico por Computador/métodos , Pólipos do Colo/diagnóstico por imagem , Pólipos do Colo/diagnóstico , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/diagnóstico por imagem , AlgoritmosRESUMO
BACKGROUND: Consumer sleep trackers (CSTs) have gained significant popularity because they enable individuals to conveniently monitor and analyze their sleep. However, limited studies have comprehensively validated the performance of widely used CSTs. Our study therefore investigated popular CSTs based on various biosignals and algorithms by assessing the agreement with polysomnography. OBJECTIVE: This study aimed to validate the accuracy of various types of CSTs through a comparison with in-lab polysomnography. Additionally, by including widely used CSTs and conducting a multicenter study with a large sample size, this study seeks to provide comprehensive insights into the performance and applicability of these CSTs for sleep monitoring in a hospital environment. METHODS: The study analyzed 11 commercially available CSTs, including 5 wearables (Google Pixel Watch, Galaxy Watch 5, Fitbit Sense 2, Apple Watch 8, and Oura Ring 3), 3 nearables (Withings Sleep Tracking Mat, Google Nest Hub 2, and Amazon Halo Rise), and 3 airables (SleepRoutine, SleepScore, and Pillow). The 11 CSTs were divided into 2 groups, ensuring maximum inclusion while avoiding interference between the CSTs within each group. Each group (comprising 8 CSTs) was also compared via polysomnography. RESULTS: The study enrolled 75 participants from a tertiary hospital and a primary sleep-specialized clinic in Korea. Across the 2 centers, we collected a total of 3890 hours of sleep sessions based on 11 CSTs, along with 543 hours of polysomnography recordings. Each CST sleep recording covered an average of 353 hours. We analyzed a total of 349,114 epochs from the 11 CSTs compared with polysomnography, where epoch-by-epoch agreement in sleep stage classification showed substantial performance variation. More specifically, the highest macro F1 score was 0.69, while the lowest macro F1 score was 0.26. Various sleep trackers exhibited diverse performances across sleep stages, with SleepRoutine excelling in the wake and rapid eye movement stages, and wearables like Google Pixel Watch and Fitbit Sense 2 showing superiority in the deep stage. There was a distinct trend in sleep measure estimation according to the type of device. Wearables showed high proportional bias in sleep efficiency, while nearables exhibited high proportional bias in sleep latency. Subgroup analyses of sleep trackers revealed variations in macro F1 scores based on factors, such as BMI, sleep efficiency, and apnea-hypopnea index, while the differences between male and female subgroups were minimal. CONCLUSIONS: Our study showed that among the 11 CSTs examined, specific CSTs showed substantial agreement with polysomnography, indicating their potential application in sleep monitoring, while other CSTs were partially consistent with polysomnography. This study offers insights into the strengths of CSTs within the 3 different classes for individuals interested in wellness who wish to understand and proactively manage their own sleep.
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Fases do Sono , Sono , Humanos , Feminino , Masculino , Estudos Prospectivos , Polissonografia , Monitores de Aptidão FísicaRESUMO
Successful ultrasound-guided supraclavicular block (SCB) requires the understanding of sonoanatomy and identification of the optimal view. Segmentation using a convolutional neural network (CNN) is limited in clearly determining the optimal view. The present study describes the development of a computer-aided diagnosis (CADx) system using a CNN that can determine the optimal view for complete SCB in real time. The aim of this study was the development of computer-aided diagnosis system that aid non-expert to determine the optimal view for complete supraclavicular block in real time. Ultrasound videos were retrospectively collected from 881 patients to develop the CADx system (600 to the training and validation set and 281 to the test set). The CADx system included classification and segmentation approaches, with Residual neural network (ResNet) and U-Net, respectively, applied as backbone networks. In the classification approach, an ablation study was performed to determine the optimal architecture and improve the performance of the model. In the segmentation approach, a cascade structure, in which U-Net is connected to ResNet, was implemented. The performance of the two approaches was evaluated based on a confusion matrix. Using the classification approach, ResNet34 and gated recurrent units with augmentation showed the highest performance, with average accuracy 0.901, precision 0.613, recall 0.757, f1-score 0.677 and AUROC 0.936. Using the segmentation approach, U-Net combined with ResNet34 and augmentation showed poorer performance than the classification approach. The CADx system described in this study showed high performance in determining the optimal view for SCB. This system could be expanded to include many anatomical regions and may have potential to aid clinicians in real-time settings.Trial registration The protocol was registered with the Clinical Trial Registry of Korea (KCT0005822, https://cris.nih.go.kr ).
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Aprendizado Profundo , Humanos , Estudos Retrospectivos , Redes Neurais de Computação , Diagnóstico por Computador , Ultrassonografia de Intervenção , Processamento de Imagem Assistida por Computador/métodosRESUMO
Chicken meat spoilage is a significant concern for food safety and quality, and this study aims to predict the spoilage point of chicken breast meat through various attributes and metabolites. Chicken meat was stored in anaerobic packaging at 4 °C for 13 days, and various meat quality attributes (pH, drip loss, color, volatile basic nitrogen [VBN], total aerobic bacteria [TAB], and metabolites) were examined. First, the spoiled point (VBN >20 mg/100 g and/or TAB >7 log CFU/g) of the chicken breast meat was determined. Using univariate and multivariate analyses, twenty-four candidate metabolites were identified. A receiver operating characteristic (ROC) analysis was used to validate the obtained binary logistic regression model using nine metabolites (proline, methionine, glutamate, threonine, acetate, uridine 5'-monophosphate, hypoxanthine, glycine, and glutamine). The results showed a high area under the ROC curve value (0.992). Thus, this study confirmed the predictability of spoilage points in chicken breast meat through these nine metabolites.
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BACKGROUND: The growing public interest and awareness regarding the significance of sleep is driving the demand for sleep monitoring at home. In addition to various commercially available wearable and nearable devices, sound-based sleep staging via deep learning is emerging as a decent alternative for their convenience and potential accuracy. However, sound-based sleep staging has only been studied using in-laboratory sound data. In real-world sleep environments (homes), there is abundant background noise, in contrast to quiet, controlled environments such as laboratories. The use of sound-based sleep staging at homes has not been investigated while it is essential for practical use on a daily basis. Challenges are the lack of and the expected huge expense of acquiring a sufficient size of home data annotated with sleep stages to train a large-scale neural network. OBJECTIVE: This study aims to develop and validate a deep learning method to perform sound-based sleep staging using audio recordings achieved from various uncontrolled home environments. METHODS: To overcome the limitation of lacking home data with known sleep stages, we adopted advanced training techniques and combined home data with hospital data. The training of the model consisted of 3 components: (1) the original supervised learning using 812 pairs of hospital polysomnography (PSG) and audio recordings, and the 2 newly adopted components; (2) transfer learning from hospital to home sounds by adding 829 smartphone audio recordings at home; and (3) consistency training using augmented hospital sound data. Augmented data were created by adding 8255 home noise data to hospital audio recordings. Besides, an independent test set was built by collecting 45 pairs of overnight PSG and smartphone audio recording at homes to examine the performance of the trained model. RESULTS: The accuracy of the model was 76.2% (63.4% for wake, 64.9% for rapid-eye movement [REM], and 83.6% for non-REM) for our test set. The macro F1-score and mean per-class sensitivity were 0.714 and 0.706, respectively. The performance was robust across demographic groups such as age, gender, BMI, or sleep apnea severity (accuracy 73.4%-79.4%). In the ablation study, we evaluated the contribution of each component. While the supervised learning alone achieved accuracy of 69.2% on home sound data, adding consistency training to the supervised learning helped increase the accuracy to a larger degree (+4.3%) than adding transfer learning (+0.1%). The best performance was shown when both transfer learning and consistency training were adopted (+7.0%). CONCLUSIONS: This study shows that sound-based sleep staging is feasible for home use. By adopting 2 advanced techniques (transfer learning and consistency training) the deep learning model robustly predicts sleep stages using sounds recorded at various uncontrolled home environments, without using any special equipment but smartphones only.
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Aprendizado Profundo , Smartphone , Humanos , Gravação de Som , Ambiente Domiciliar , Fases do Sono , SonoRESUMO
OBJECTIVE: This study aimed to evaluate the physicochemical, metabolomic, and sensory qualities of Chikso and Hanwoo beef during 28 days of wet aging. METHODS: Rump and loins from Hanwoo and Chikso were obtained and wet-aged for 28 days at 4°C. The samples were collected at 7-day interval (n = 3 for each period). Physicochemical qualities including pH, meat color, shear force value, and myofibrillar fragmentation index, metabolomic profiles, and sensory attributes (volatile organic compounds and relative taste intensities) were measured. RESULTS: Chikso showed a significantly higher shear force value than Hanwoo on day 0; however, no differences between breeds were found after day 14, regardless of the cuts. Overall, Chikso had more abundant metabolites than Hanwoo, especially L-carnitine and tyrosine. Among the volatiles, the ketone ratio was higher in the Chikso rump than the Hanwoo rump; however, Chikso had fewer alcohols and aldehydes than Hanwoo. Chikso rump showed higher taste intensities than the Hanwoo rump on day 0, and sourness decreased in Chikso, but increased in the Hanwoo rump on day 14. Wet aging for 14 days intensified the taste of Chikso loin but reduced the umami intensity of Hanwoo loin. CONCLUSION: Chikso had different metabolomic and sensory characteristics compared to Hanwoo cattle, and 14 days of wet aging could improve its tenderness and flavor traits.
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BACKGROUND: Multinight monitoring can be helpful for the diagnosis and management of obstructive sleep apnea (OSA). For this purpose, it is necessary to be able to detect OSA in real time in a noisy home environment. Sound-based OSA assessment holds great potential since it can be integrated with smartphones to provide full noncontact monitoring of OSA at home. OBJECTIVE: The purpose of this study is to develop a predictive model that can detect OSA in real time, even in a home environment where various noises exist. METHODS: This study included 1018 polysomnography (PSG) audio data sets, 297 smartphone audio data sets synced with PSG, and a home noise data set containing 22,500 noises to train the model to predict breathing events, such as apneas and hypopneas, based on breathing sounds that occur during sleep. The whole breathing sound of each night was divided into 30-second epochs and labeled as "apnea," "hypopnea," or "no-event," and the home noises were used to make the model robust to a noisy home environment. The performance of the prediction model was assessed using epoch-by-epoch prediction accuracy and OSA severity classification based on the apnea-hypopnea index (AHI). RESULTS: Epoch-by-epoch OSA event detection showed an accuracy of 86% and a macro F1-score of 0.75 for the 3-class OSA event detection task. The model had an accuracy of 92% for "no-event," 84% for "apnea," and 51% for "hypopnea." Most misclassifications were made for "hypopnea," with 15% and 34% of "hypopnea" being wrongly predicted as "apnea" and "no-event," respectively. The sensitivity and specificity of the OSA severity classification (AHI≥15) were 0.85 and 0.84, respectively. CONCLUSIONS: Our study presents a real-time epoch-by-epoch OSA detector that works in a variety of noisy home environments. Based on this, additional research is needed to verify the usefulness of various multinight monitoring and real-time diagnostic technologies in the home environment.
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Síndromes da Apneia do Sono , Apneia Obstrutiva do Sono , Humanos , Sons Respiratórios , Apneia Obstrutiva do Sono/diagnóstico , Sono , AlgoritmosRESUMO
The formation of biomolecular condensates mediated by a coupling of associative and segregative phase transitions plays a critical role in controlling diverse cellular functions in nature. This has inspired the use of phase transitions to design synthetic systems. While design rules of phase transitions have been established for many synthetic intrinsically disordered proteins, most efforts have focused on investigating their phase behaviors in a test tube. Here, we present a rational engineering approach to program the formation and physical properties of synthetic condensates to achieve intended cellular functions. We demonstrate this approach through targeted plasmid sequestration and transcription regulation in bacteria and modulation of a protein circuit in mammalian cells. Our approach lays the foundation for engineering designer condensates for synthetic biology applications.
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Condensados Biomoleculares , Proteínas Intrinsicamente Desordenadas , Animais , Organelas/metabolismo , Proteínas Intrinsicamente Desordenadas/metabolismo , MamíferosRESUMO
Many synthetic biology applications rely on programming living cells using gene circuits - the assembly and wiring of genetic elements to control cellular behaviors. Extensive progress has been made in constructing gene circuits with diverse functions and applications. For many circuit functions, however, it remains challenging to ensure that the circuits operate in a predictable manner. Although the notion of predictability may appear intuitive, close inspection suggests that it is not always clear what constitutes predictability. We dissect this concept and how it can be confounded by the complexity of a circuit, the complexity of the context, and the interplay between the two. We discuss circuit engineering strategies, in both computation and experiment, that have been used to improve the predictability of gene circuits.
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Redes Reguladoras de Genes , Biologia Sintética , Engenharia GenéticaRESUMO
Objective assessment of atopic dermatitis (AD) is essential for choosing proper management strategies. This study investigated the performance of convolutional neural networks (CNN) models in grading the severity of AD. Five board-certified dermatologists independently evaluated the severity of 9,192 AD images. The severity of AD was evaluated based on an Investigator's Global Assessment (IGA) and six signs of AD. For CNN training, we applied three distinct approaches: 1) ensemble vs. integration 2) hard-label vs. soft-label and 3) train-set pruning. For the IGA prediction, the two best models were chosen based on the macro-averaged AUROC and F-1 score. The ensemble-soft-label-pruning model was chosen based on AUROC 0.943, 0.927 for the internal and external validation set respectively, and integration-soft-label-whole dataset model was chosen based on the F1-score 0.750, 0.721 for the internal and external validation set respectively. CNN models trained by multi-evaluator dataset outperformed the models by an individual evaluator dataset, and they performed better to the dataset in which the assessment of dermatologists was concordant. In conclusion, CNN models for AD could be improved by labeled dataset from multiple evaluators, merging methods with soft-label and train-set pruning.
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Dermatite Atópica , Humanos , Redes Neurais de Computação , Imunoglobulina ARESUMO
We identified key metabolites reflecting microbial spoilage and differentiated unfrozen meat from frozen/thawed (FT) using 2D qNMR analysis. Unfrozen and FT chicken breasts were prepared, individually aerobically packaged, and stored for 16 days at 2 °C. Only volatile basic nitrogen (VBN) was significantly changed after 6 log CFU/g of total aerobic bacteria (p < 0.05). Extended storage resulted in an increase in organic acids, free amino acids, biogenic amines, and hypoxanthine and a decrease in N,N-dimethylglycine, inosine 5'-monophosphate, and proline. Acetic acid demonstrated the highest correlation with VBN (r = 0.97). Unfrozen and FT breast meat can be differentiated by uniform concentration of carnosine, ß-alanine, and histidine levels, consistent changes in nucleotides by storage time, and changes in microbial metabolism patterns that are reflected by some free amino acids. Thus, NMR-based metabolomics can be used to evaluate chicken breast meat freshness and distinguish between unfrozen and FT meat.