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  • We present a method for predicting dense depth in scenarios where both a monocular camera and people in the scene are freely moving. Existing methods for recovering depth for dynamic, non-rigid objects from monocular video impose strong assumptions on the objects' motion and may only recover sparse depth. In this paper, we take a data-driven approach and learn human depth priors from a new source of data thousands of Internet videos of people imitating mannequins, i.e., freezing in diverse, natural poses, while a hand-held camera tours the scene. Because people are stationary, training data can be generated using multi-view stereo reconstruction. At inference time, our method uses motion parallax cues from the static areas of the scenes to guide the depth prediction. We demonstrate our method on real-world sequences of complex human actions captured by a moving hand-held camera, show improvement over state-of-the-art monocular depth prediction methods, and show various 3D effects produced using our predicted depth.Multi-label classification is an important research topic in machine learning, for which exploiting label dependency is an effective modeling principle. Recently, probabilistic models have shown great potential in discovering dependencies among labels. In this paper, motivated by the recent success of multi-view learning to improve the generalization performance, we propose a novel multi-view probabilistic model named latent conditional Bernoulli mixture (LCBM) for multi-label classification. The LCBM is a generative model taking features from different views as inputs, and conditional on the latent subspace shared by the views a Bernoulli mixture model is adopted to build label dependency. Inside each component of the mixture, the labels have a weak correlation which facilitates computational convenience. The mean field variational inference framework is used to carry out approximate posterior inference in the probabilistic model, where we propose a Gaussian mixture variational autoencoder (GMVAE) for effective posterior approximation. We further develop a scalable stochastic training algorithm for efficiently optimizing the model parameters and variational parameters, and derive an efficient prediction procedure based on greedy search. Experimental results on multiple benchmark datasets show that our approach outperforms other state-of-the-art methods under various metrics.This paper introduces a novel depth recovery method based on light absorption in water. Water absorbs light at almost all wavelengths whose absorption coefficient is related to the wavelength. Based on the Beer-Lambert model, we introduce a bispectral depth recovery method that leverages the light absorption difference between two near-infrared wavelengths captured with a distant point source and orthographic cameras. Through extensive analysis, we show that accurate depth can be recovered irrespective of the surface texture and reflectance, and introduce algorithms to correct for nonidealities of a practical implementation including tilted light source and camera placement, nonideal bandpass filters and the perspective effect of the camera with a diverging point light source. We construct a coaxial bispectral depth imaging system using low-cost off-the-shelf hardware and demonstrate its use for recovering the shapes of complex and dynamic objects in water. We also present a trispectral variant to further improve robustness to extremely challenging surface reflectance. Experimental results validate the theory and practical implementation of this novel depth recovery paradigm, which we refer to as shape from water.Grounding referring expressions in images aims to locate the object instance in an image described by a referring expression. It involves a joint understanding of natural language and image content and is essential for a range of visual tasks related to human-computer interaction. As a language-to-vision matching task, the core of this problem is to not only extract all the necessary information in both the image and referring expressions, but also to to make full use of context information to achieve alignment of cross-modal semantic concepts in the extracted information. In this paper, we propose a Cross-Modal Relationship Extractor (CMRE) to adaptively highlight objects and relationships related to the given expression, with a cross-modal attention mechanism, and represent the extracted information as language-guided visual relation graphs. In addition, we propose a Gated Graph Convolutional Network (GGCN) to compute multimodal semantic context by fusing information from different modes and propagating multimodal information in the structured relation graphs. Experimental results on three common benchmark datasets show that our Cross-Modal Relationship Inference Network, which consists of CMRE and GGCN, greatly surpass all existing state-of-the-art methods.OBJECTIVE Treatment of brain tumors requires high precision in order to ensure sufficient treatment while minimizing damage to surrounding healthy tissue. Ablation of such tumors using needle-based therapeutic ultrasound (NBTU) under real-time magnetic resonance imaging (MRI) can fulfill this need. https://www.selleckchem.com/products/ew-7197.html However, the constrained space and strong magnetic field in the MRI bore restricts patient access limiting precise placement of the NBTU ablation tool. A surgical robot compatible with use inside the bore of an MRI scanner can alleviate these challenges. METHODS We present preclinical trials of a robotic system for NBTU ablation of brain tumors under real-time MRI guidance. The system comprises of an updated robotic manipulator and corresponding control electronics, the NBTU ablation system and applications for planning, navigation and monitoring of the system. RESULTS The robotic system had a mean translational and rotational accuracy of 1.39±0.64 mm and 1.27±0.56° in gelatin phantoms and 3.13±1.41 mm and 5.58±3.59° in 10 porcine trials while causing a maximum reduction in signal to noise ratio (SNR) of 10.3%. CONCLUSION The integrated robotic system can place NBTU ablator at a desired target location in porcine brain and monitor the ablation in realtime via magnetic resonance thermal imaging (MRTI). SIGNIFICANCE Further optimization of this system could result in a clinically viable system for use in human trials for various diagnostic or therapeutic neurosurgical interventions.
    We present a method for predicting dense depth in scenarios where both a monocular camera and people in the scene are freely moving. Existing methods for recovering depth for dynamic, non-rigid objects from monocular video impose strong assumptions on the objects' motion and may only recover sparse depth. In this paper, we take a data-driven approach and learn human depth priors from a new source of data thousands of Internet videos of people imitating mannequins, i.e., freezing in diverse, natural poses, while a hand-held camera tours the scene. Because people are stationary, training data can be generated using multi-view stereo reconstruction. At inference time, our method uses motion parallax cues from the static areas of the scenes to guide the depth prediction. We demonstrate our method on real-world sequences of complex human actions captured by a moving hand-held camera, show improvement over state-of-the-art monocular depth prediction methods, and show various 3D effects produced using our predicted depth.Multi-label classification is an important research topic in machine learning, for which exploiting label dependency is an effective modeling principle. Recently, probabilistic models have shown great potential in discovering dependencies among labels. In this paper, motivated by the recent success of multi-view learning to improve the generalization performance, we propose a novel multi-view probabilistic model named latent conditional Bernoulli mixture (LCBM) for multi-label classification. The LCBM is a generative model taking features from different views as inputs, and conditional on the latent subspace shared by the views a Bernoulli mixture model is adopted to build label dependency. Inside each component of the mixture, the labels have a weak correlation which facilitates computational convenience. The mean field variational inference framework is used to carry out approximate posterior inference in the probabilistic model, where we propose a Gaussian mixture variational autoencoder (GMVAE) for effective posterior approximation. We further develop a scalable stochastic training algorithm for efficiently optimizing the model parameters and variational parameters, and derive an efficient prediction procedure based on greedy search. Experimental results on multiple benchmark datasets show that our approach outperforms other state-of-the-art methods under various metrics.This paper introduces a novel depth recovery method based on light absorption in water. Water absorbs light at almost all wavelengths whose absorption coefficient is related to the wavelength. Based on the Beer-Lambert model, we introduce a bispectral depth recovery method that leverages the light absorption difference between two near-infrared wavelengths captured with a distant point source and orthographic cameras. Through extensive analysis, we show that accurate depth can be recovered irrespective of the surface texture and reflectance, and introduce algorithms to correct for nonidealities of a practical implementation including tilted light source and camera placement, nonideal bandpass filters and the perspective effect of the camera with a diverging point light source. We construct a coaxial bispectral depth imaging system using low-cost off-the-shelf hardware and demonstrate its use for recovering the shapes of complex and dynamic objects in water. We also present a trispectral variant to further improve robustness to extremely challenging surface reflectance. Experimental results validate the theory and practical implementation of this novel depth recovery paradigm, which we refer to as shape from water.Grounding referring expressions in images aims to locate the object instance in an image described by a referring expression. It involves a joint understanding of natural language and image content and is essential for a range of visual tasks related to human-computer interaction. As a language-to-vision matching task, the core of this problem is to not only extract all the necessary information in both the image and referring expressions, but also to to make full use of context information to achieve alignment of cross-modal semantic concepts in the extracted information. In this paper, we propose a Cross-Modal Relationship Extractor (CMRE) to adaptively highlight objects and relationships related to the given expression, with a cross-modal attention mechanism, and represent the extracted information as language-guided visual relation graphs. In addition, we propose a Gated Graph Convolutional Network (GGCN) to compute multimodal semantic context by fusing information from different modes and propagating multimodal information in the structured relation graphs. Experimental results on three common benchmark datasets show that our Cross-Modal Relationship Inference Network, which consists of CMRE and GGCN, greatly surpass all existing state-of-the-art methods.OBJECTIVE Treatment of brain tumors requires high precision in order to ensure sufficient treatment while minimizing damage to surrounding healthy tissue. Ablation of such tumors using needle-based therapeutic ultrasound (NBTU) under real-time magnetic resonance imaging (MRI) can fulfill this need. https://www.selleckchem.com/products/ew-7197.html However, the constrained space and strong magnetic field in the MRI bore restricts patient access limiting precise placement of the NBTU ablation tool. A surgical robot compatible with use inside the bore of an MRI scanner can alleviate these challenges. METHODS We present preclinical trials of a robotic system for NBTU ablation of brain tumors under real-time MRI guidance. The system comprises of an updated robotic manipulator and corresponding control electronics, the NBTU ablation system and applications for planning, navigation and monitoring of the system. RESULTS The robotic system had a mean translational and rotational accuracy of 1.39±0.64 mm and 1.27±0.56° in gelatin phantoms and 3.13±1.41 mm and 5.58±3.59° in 10 porcine trials while causing a maximum reduction in signal to noise ratio (SNR) of 10.3%. CONCLUSION The integrated robotic system can place NBTU ablator at a desired target location in porcine brain and monitor the ablation in realtime via magnetic resonance thermal imaging (MRTI). SIGNIFICANCE Further optimization of this system could result in a clinically viable system for use in human trials for various diagnostic or therapeutic neurosurgical interventions.
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  • The HPLC examination of the methanol concentrate of the plant demonstrated the occurrence of different phenolic acids and flavonoids like caffeic acid (145.96μg/100mg DE), syringic acid (125.85 μg/100mg DE), ferulic acid (155.89 μg/100mg DE), apigenin (28.43 μg/100mg DE), kaempferol (53.41 μg/100mg DE) etc. in various amounts. The consequences of haemolytic lethality, cytotoxicity and genotoxicity of fluid concentrates of the edible plant ensure the security at cell and genomic level. The fluid concentrate of the plant fundamentally repressed DNA harm and these information recommend that the watery concentrate of L. cubeba can forestall oxidative DNA harm to rodent lymphocytes, which is likely because of antioxidant constituents in the concentrate. These outcomes demonstrate that L. cubeba can be utilized in dietary applications with a possibility to diminish oxidative pressure. © 2020 The Authors.This research aims to define the depth of Moho in Iran by collocation method using gravimetric data with seismic information. The definition of the Moho in the Iranian region is of considerable importance due to the geological complexity of the area also characterized by tectonic and orogenic events of particular uniqueness. We applied the collocation method to Moho recovery using the gravity data generated by GOCO03S model reduced by topography/bathymetry, sediment and consolidated crust effects from CRUST1.0. These data have been complemented with seismic Moho depth estimates. A compilation of 213-points seismic depth has been collected over Iran and used in the integrated gravimetric-seismic inversion. Among them, 140 seismic points have been selected completely random and included as data in the integrated collocation approach for Moho depth estimation. The 73 remaining seismic points have been used as checking points for validating the estimated Moho. In the first run, gravity data only have been considered to collocation Moho recovery. When comparing this gravimetric solution with the 73 seismic checking points, a standard deviation of 6.2 km was found. In case of considering the regional seismic depths into the collocation approach, the standard deviation of the residuals between our results and seismic checking Moho depths improved to 4.9 km. It must be stated that, even in the integrated inversion, a significant discrepancy between the seismic and the integrated gravimetric-seismic Moho is present in the South Caspian Basin. Low quality of CRUST1.0 could explain this inconsistency in this area. © 2020 The Author(s).Lysosomal storage diseases (LSDs) are a group of about 50 inborn errors of metabolism characterized by the lysosomal accumulation of partially or non-degraded molecules due to mutations in proteins involved in the degradation of macromolecules, transport, lysosomal biogenesis or modulators of lysosomal environment. Significant advances have been achieved in the diagnosis, management, and treatment of LSDs patients. In terms of approved therapies, these include enzyme replacement therapy (ERT), substrate reduction therapy, hematopoietic stem cell transplantation, and pharmacological chaperone therapy. In this review, we summarize the Colombian experience in LSDs thorough the evidence published. We identified 113 articles published between 1995 and 2019 that included Colombian researchers or physicians, and which were mainly focused in Mucopolysaccharidoses, Pompe disease, Gaucher disease, Fabry disease, and Tay-Sachs and Sandhoff diseases. Most of these articles focused on basic research, clinical cases, and mutation reports. Noteworthy, implementation of the enzyme assay in dried blood samples, led to a 5-fold increase in the identification of LSD patients, suggesting that these disorders still remain undiagnosed in the country. We consider that the information presented in this review will contribute to the knowledge of a broad spectrum of LSDs in Colombia and will also contribute to the development of public policies and the identification of research opportunities. © 2020 The Author(s).A raw Moroccan clay locally named "Ghassoul" (Gh) was characterized using several techniques such as Fourier Transform Infrared Spectroscopy (FTIR), X-Ray Diffraction (XRD), Brunauer, Emmett and Teller method (BET), Scanning Electron Microscopy (SEM) and simultaneous Thermo-Gravimetric and Differential Thermal Analysis (TGA/DTA). These techniques indicate that the Gh consists essentially of steveniste, calcite, dolomite and quartz. The study of the interfacial electrochemical properties of Gh in different solutions of electrolyte salts (NaCl, CsCl, NaF, NaBr and LiCl) was carried out using the potentiometric and conductometric titrations It was shown that the Gh particles were stable in aqueous phase within the pH range (3-12) and the point of zero charge (PZC) was located at pH = 10.7. The adsorption sequence, carried out at various ionic strengths, showed that the adsorption mechanism onto the Gh particles is both electrostatic and specific at pH below the pHpzc, while at a pH range greater than the pHpzc the mechanism is electrostatic in nature. https://www.selleckchem.com/products/Tretinoin(Aberela).html The total number of surface sites, determined using the graphical extrapolation method, was 11OH/nm2. Ionization constants ( p K int + and p K int - ) in the presence of various electrolytes have also been determined and their values are 10.08 and 12.38, respectively. © 2020 Published by Elsevier Ltd.The growing interest in bioactive compounds, especially in polyphenols, is due to their abundance in the human diet and potentially positive effects on health. The consumption of polyphenols has been shown to possess anti-diabetic properties by preventing insulin resistance or insulin secretion through different signaling pathways, this effect is associated with their capacity to exert genomic modulations. Several studies have suggested that polyphenols could also bind to cellular proteins and modulate their activity, however, the mechanisms of action underlying their beneficial effects are complex and are not fully understood. The aim of this work was to characterize phenolic compounds present in blue corn and black bean extracts as well as identify their potential interactions with target proteins involved in diabetes pathogenesis using in silico approach. Total polyphenols content of both blue corn and black beans was identified using UPLC-ESI/qTOF/MS and quantified by colorimetric assays. In this work we identified twenty-eight phenolic compounds in the extracts, mainly anthocyanins, flavonols, hydroxycinamic acids, dihydroxybenzoic acids, flavones, isoflavones, and flavanols.
    The HPLC examination of the methanol concentrate of the plant demonstrated the occurrence of different phenolic acids and flavonoids like caffeic acid (145.96μg/100mg DE), syringic acid (125.85 μg/100mg DE), ferulic acid (155.89 μg/100mg DE), apigenin (28.43 μg/100mg DE), kaempferol (53.41 μg/100mg DE) etc. in various amounts. The consequences of haemolytic lethality, cytotoxicity and genotoxicity of fluid concentrates of the edible plant ensure the security at cell and genomic level. The fluid concentrate of the plant fundamentally repressed DNA harm and these information recommend that the watery concentrate of L. cubeba can forestall oxidative DNA harm to rodent lymphocytes, which is likely because of antioxidant constituents in the concentrate. These outcomes demonstrate that L. cubeba can be utilized in dietary applications with a possibility to diminish oxidative pressure. © 2020 The Authors.This research aims to define the depth of Moho in Iran by collocation method using gravimetric data with seismic information. The definition of the Moho in the Iranian region is of considerable importance due to the geological complexity of the area also characterized by tectonic and orogenic events of particular uniqueness. We applied the collocation method to Moho recovery using the gravity data generated by GOCO03S model reduced by topography/bathymetry, sediment and consolidated crust effects from CRUST1.0. These data have been complemented with seismic Moho depth estimates. A compilation of 213-points seismic depth has been collected over Iran and used in the integrated gravimetric-seismic inversion. Among them, 140 seismic points have been selected completely random and included as data in the integrated collocation approach for Moho depth estimation. The 73 remaining seismic points have been used as checking points for validating the estimated Moho. In the first run, gravity data only have been considered to collocation Moho recovery. When comparing this gravimetric solution with the 73 seismic checking points, a standard deviation of 6.2 km was found. In case of considering the regional seismic depths into the collocation approach, the standard deviation of the residuals between our results and seismic checking Moho depths improved to 4.9 km. It must be stated that, even in the integrated inversion, a significant discrepancy between the seismic and the integrated gravimetric-seismic Moho is present in the South Caspian Basin. Low quality of CRUST1.0 could explain this inconsistency in this area. © 2020 The Author(s).Lysosomal storage diseases (LSDs) are a group of about 50 inborn errors of metabolism characterized by the lysosomal accumulation of partially or non-degraded molecules due to mutations in proteins involved in the degradation of macromolecules, transport, lysosomal biogenesis or modulators of lysosomal environment. Significant advances have been achieved in the diagnosis, management, and treatment of LSDs patients. In terms of approved therapies, these include enzyme replacement therapy (ERT), substrate reduction therapy, hematopoietic stem cell transplantation, and pharmacological chaperone therapy. In this review, we summarize the Colombian experience in LSDs thorough the evidence published. We identified 113 articles published between 1995 and 2019 that included Colombian researchers or physicians, and which were mainly focused in Mucopolysaccharidoses, Pompe disease, Gaucher disease, Fabry disease, and Tay-Sachs and Sandhoff diseases. Most of these articles focused on basic research, clinical cases, and mutation reports. Noteworthy, implementation of the enzyme assay in dried blood samples, led to a 5-fold increase in the identification of LSD patients, suggesting that these disorders still remain undiagnosed in the country. We consider that the information presented in this review will contribute to the knowledge of a broad spectrum of LSDs in Colombia and will also contribute to the development of public policies and the identification of research opportunities. © 2020 The Author(s).A raw Moroccan clay locally named "Ghassoul" (Gh) was characterized using several techniques such as Fourier Transform Infrared Spectroscopy (FTIR), X-Ray Diffraction (XRD), Brunauer, Emmett and Teller method (BET), Scanning Electron Microscopy (SEM) and simultaneous Thermo-Gravimetric and Differential Thermal Analysis (TGA/DTA). These techniques indicate that the Gh consists essentially of steveniste, calcite, dolomite and quartz. The study of the interfacial electrochemical properties of Gh in different solutions of electrolyte salts (NaCl, CsCl, NaF, NaBr and LiCl) was carried out using the potentiometric and conductometric titrations It was shown that the Gh particles were stable in aqueous phase within the pH range (3-12) and the point of zero charge (PZC) was located at pH = 10.7. The adsorption sequence, carried out at various ionic strengths, showed that the adsorption mechanism onto the Gh particles is both electrostatic and specific at pH below the pHpzc, while at a pH range greater than the pHpzc the mechanism is electrostatic in nature. https://www.selleckchem.com/products/Tretinoin(Aberela).html The total number of surface sites, determined using the graphical extrapolation method, was 11OH/nm2. Ionization constants ( p K int + and p K int - ) in the presence of various electrolytes have also been determined and their values are 10.08 and 12.38, respectively. © 2020 Published by Elsevier Ltd.The growing interest in bioactive compounds, especially in polyphenols, is due to their abundance in the human diet and potentially positive effects on health. The consumption of polyphenols has been shown to possess anti-diabetic properties by preventing insulin resistance or insulin secretion through different signaling pathways, this effect is associated with their capacity to exert genomic modulations. Several studies have suggested that polyphenols could also bind to cellular proteins and modulate their activity, however, the mechanisms of action underlying their beneficial effects are complex and are not fully understood. The aim of this work was to characterize phenolic compounds present in blue corn and black bean extracts as well as identify their potential interactions with target proteins involved in diabetes pathogenesis using in silico approach. Total polyphenols content of both blue corn and black beans was identified using UPLC-ESI/qTOF/MS and quantified by colorimetric assays. In this work we identified twenty-eight phenolic compounds in the extracts, mainly anthocyanins, flavonols, hydroxycinamic acids, dihydroxybenzoic acids, flavones, isoflavones, and flavanols.
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  • Being classified within the Basidiomycota, Auricularia polytricha has been proved to degrade lignocellulose, a major component of wheat bran fiber. During the fermentation of lignocellulose by A. polytricha strain, a large number of intermediate products are produced, which affect the further degradation of lignocellulose. Therefore, it is essential to analyze the fermentation intermediates for study on the degradation mechanism of wheat bran fiber. In this study, the effectiveness of fermentation of wheat bran fiber by A. polytricha strain was confirmed via scanning electron microscopy. Additionally, the results of gas chromatography-mass spectrometry indicated that the A. polytricha strain could degrade wheat bran fiber and produce several aromatic compounds, and that the number of products obtained after 7 days of fermentation was significantly lower than that after 3 days of fermentation. It has also been demonstrated that diisooctyl phthalate and 9-octadecenamide belong to metabolites produced during the fermentation of wheat bran fiber, by culturing A. polytricha with wheat bran fiber and glucose as carbon source, respectively. Moreover, by conducting an ultraviolet wavelength scanning of the culture liquid containing vanillin fermented by A. polytricha, it has been indicated that the strain could degrade vanillin and further demonstrated that the strain has the ability to degrade wheat bran fiber. Furthermore, adding the products of wheat bran fiber fermented for 3 days by A. polytricha could improve the elasticity of the dough sheet. © 2020 The Authors. Food Science & Nutrition published by Wiley Periodicals, Inc.The Caribbean island of Barbados has a high burden of diabetes and cardiovascular disease. Dietary habits were last described in 2005. A representative population-based sample (n = 363, aged 25-64 years) provided two nonconsecutive 24-hr dietary recalls in this cross-sectional study. https://www.selleckchem.com/products/sr-4835.html Mean daily nutrient intakes were compared with the Dietary Guidelines for Americans. Subgroup differences by age, sex, and educational level were examined using logistic regression. High sugar intakes exist for both sexes with 24% (95% CIs 18.9, 30.0) consuming less than the recommended less then 10% of energy from added sugars (men 22%; 15.0, 31.6; women 26%; 18.9, 33.7). Sugar-sweetened beverages provide 43% (42.2%, 44.4%) of total sugar intake. Inadequate dietary fiber intakes (men 21 g, 18.2, 22.8; women 18 g, 16.7, 18.9) exist across all age groups. Inadequate micronutrient intake was found in women for calcium, folate, thiamine, zinc, and iron. Older persons (aged 45-64 years) were more likely to report adequacy of dietary fiber (OR = 2.7, 1.5, 4.8) and iron (OR = 3.0, 1.7, 5.3) than younger persons (aged 25-44). Older persons (aged 45-64 years) were less likely to have an adequate supply of riboflavin (OR = 0.4, 0.2, 0.6) than younger persons. Men were more likely to have adequate intakes of iron (OR = 13.0, 6.1, 28.2), folate (OR = 2.4, 1.3, 4.6), and thiamine (OR = 3.0, 1.5, 5.0) than women. Education was not associated with nutrient intake. The Barbadian diet is characterized by high sugar intakes and inadequate dietary fiber; a nutrient profile associated with an increased risk of obesity, type 2 diabetes, and related noncommunicable diseases. © 2020 The Authors. Food Science & Nutrition published by Wiley Periodicals, Inc.This study evaluated the incorporation of microcapsules containing nisin and avocado peel extract on the shelf life of ground beef. Ten treatments were studied and divided into two groups one packaged under vacuum and the other in permeable packaging. Each group contained (a) control, (b) extract, (c) nisin, (d) empty microcapsules (only wall microcapsule system), and (e) microcapsules with extract and nisin. The samples containing the microcapsules presented lower bacterial growth and less oxidation. On day 10, the vacuum-packaged samples with microencapsulated preservative presented a reduction in the oxidation of proteins of approximately 45%, of 30% in the growth of mesophiles, and of 38% in the growth of coliforms, as well as a reduction in the changes in the pH and ɑ W that occur during storage, compared with the permeable control. The combination of microcapsules with vacuum packaging reduced the physicochemical and microbiological changes that occur in the controls. © 2020 The Authors. Food Science & Nutrition published by Wiley Periodicals, Inc.Scope Phaseolus vulgaris L. is rich in alpha-amylase inhibitor and has been used for reducing glycemia and calories absorption through preventing or delaying the digestion of complex carbohydrate. A randomized, double-blinded, placebo-controlled study was conducted on obese volunteers to evaluate the degree of significate weight loss by regular intake Phaseolus vulgaris cultivated from Southwestern region of China. Method The volunteers were divided into two groups, homogeneous for age, gender, and body weight. Phaseolus vulgaris extract or placebo was given 2,400 mg per day before each daily meal for 35 consecutive days. Each subject's body weight, fat mass, body mass index, blood biochemical parameters, skinfold fat thickness, and waist/hip circumferences were monitored and analyzed. Result and conclusion As a result, the average amount of weight lost by the Phaseolus vulgaris extract group was 2.24 kg (average of 0.448 kg per week), compared with a 0.29 kg weight loss (average of 0.058 kg per week) in placebo group after 35 days. The differences between groups were significant (p  less then  .01). The body mass index decreased by an average of 0.79, and the body fat decreased by 1.53% on average compared to baseline (p  less then  .05). The thickness of subcutaneous fat was significantly reduced at the four measurement points, and the decrease of waist circumference and hip circumference was significant as well. No adverse or side effects were observed during the trial period. The results indicate that Phaseolus vulgaris extract can significantly induce weight loss in a short time period. © 2019 The Authors. Food Science & Nutrition published by Wiley Periodicals, Inc.
    Being classified within the Basidiomycota, Auricularia polytricha has been proved to degrade lignocellulose, a major component of wheat bran fiber. During the fermentation of lignocellulose by A. polytricha strain, a large number of intermediate products are produced, which affect the further degradation of lignocellulose. Therefore, it is essential to analyze the fermentation intermediates for study on the degradation mechanism of wheat bran fiber. In this study, the effectiveness of fermentation of wheat bran fiber by A. polytricha strain was confirmed via scanning electron microscopy. Additionally, the results of gas chromatography-mass spectrometry indicated that the A. polytricha strain could degrade wheat bran fiber and produce several aromatic compounds, and that the number of products obtained after 7 days of fermentation was significantly lower than that after 3 days of fermentation. It has also been demonstrated that diisooctyl phthalate and 9-octadecenamide belong to metabolites produced during the fermentation of wheat bran fiber, by culturing A. polytricha with wheat bran fiber and glucose as carbon source, respectively. Moreover, by conducting an ultraviolet wavelength scanning of the culture liquid containing vanillin fermented by A. polytricha, it has been indicated that the strain could degrade vanillin and further demonstrated that the strain has the ability to degrade wheat bran fiber. Furthermore, adding the products of wheat bran fiber fermented for 3 days by A. polytricha could improve the elasticity of the dough sheet. © 2020 The Authors. Food Science & Nutrition published by Wiley Periodicals, Inc.The Caribbean island of Barbados has a high burden of diabetes and cardiovascular disease. Dietary habits were last described in 2005. A representative population-based sample (n = 363, aged 25-64 years) provided two nonconsecutive 24-hr dietary recalls in this cross-sectional study. https://www.selleckchem.com/products/sr-4835.html Mean daily nutrient intakes were compared with the Dietary Guidelines for Americans. Subgroup differences by age, sex, and educational level were examined using logistic regression. High sugar intakes exist for both sexes with 24% (95% CIs 18.9, 30.0) consuming less than the recommended less then 10% of energy from added sugars (men 22%; 15.0, 31.6; women 26%; 18.9, 33.7). Sugar-sweetened beverages provide 43% (42.2%, 44.4%) of total sugar intake. Inadequate dietary fiber intakes (men 21 g, 18.2, 22.8; women 18 g, 16.7, 18.9) exist across all age groups. Inadequate micronutrient intake was found in women for calcium, folate, thiamine, zinc, and iron. Older persons (aged 45-64 years) were more likely to report adequacy of dietary fiber (OR = 2.7, 1.5, 4.8) and iron (OR = 3.0, 1.7, 5.3) than younger persons (aged 25-44). Older persons (aged 45-64 years) were less likely to have an adequate supply of riboflavin (OR = 0.4, 0.2, 0.6) than younger persons. Men were more likely to have adequate intakes of iron (OR = 13.0, 6.1, 28.2), folate (OR = 2.4, 1.3, 4.6), and thiamine (OR = 3.0, 1.5, 5.0) than women. Education was not associated with nutrient intake. The Barbadian diet is characterized by high sugar intakes and inadequate dietary fiber; a nutrient profile associated with an increased risk of obesity, type 2 diabetes, and related noncommunicable diseases. © 2020 The Authors. Food Science & Nutrition published by Wiley Periodicals, Inc.This study evaluated the incorporation of microcapsules containing nisin and avocado peel extract on the shelf life of ground beef. Ten treatments were studied and divided into two groups one packaged under vacuum and the other in permeable packaging. Each group contained (a) control, (b) extract, (c) nisin, (d) empty microcapsules (only wall microcapsule system), and (e) microcapsules with extract and nisin. The samples containing the microcapsules presented lower bacterial growth and less oxidation. On day 10, the vacuum-packaged samples with microencapsulated preservative presented a reduction in the oxidation of proteins of approximately 45%, of 30% in the growth of mesophiles, and of 38% in the growth of coliforms, as well as a reduction in the changes in the pH and ɑ W that occur during storage, compared with the permeable control. The combination of microcapsules with vacuum packaging reduced the physicochemical and microbiological changes that occur in the controls. © 2020 The Authors. Food Science & Nutrition published by Wiley Periodicals, Inc.Scope Phaseolus vulgaris L. is rich in alpha-amylase inhibitor and has been used for reducing glycemia and calories absorption through preventing or delaying the digestion of complex carbohydrate. A randomized, double-blinded, placebo-controlled study was conducted on obese volunteers to evaluate the degree of significate weight loss by regular intake Phaseolus vulgaris cultivated from Southwestern region of China. Method The volunteers were divided into two groups, homogeneous for age, gender, and body weight. Phaseolus vulgaris extract or placebo was given 2,400 mg per day before each daily meal for 35 consecutive days. Each subject's body weight, fat mass, body mass index, blood biochemical parameters, skinfold fat thickness, and waist/hip circumferences were monitored and analyzed. Result and conclusion As a result, the average amount of weight lost by the Phaseolus vulgaris extract group was 2.24 kg (average of 0.448 kg per week), compared with a 0.29 kg weight loss (average of 0.058 kg per week) in placebo group after 35 days. The differences between groups were significant (p  less then  .01). The body mass index decreased by an average of 0.79, and the body fat decreased by 1.53% on average compared to baseline (p  less then  .05). The thickness of subcutaneous fat was significantly reduced at the four measurement points, and the decrease of waist circumference and hip circumference was significant as well. No adverse or side effects were observed during the trial period. The results indicate that Phaseolus vulgaris extract can significantly induce weight loss in a short time period. © 2019 The Authors. Food Science & Nutrition published by Wiley Periodicals, Inc.
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  • 9 years) were analyzed. Mean arterial BP increased from 83 ± 12 mm Hg to 87 ± 12 mm Hg (p = 0.0009) during the CPT. Whole-brain analysis revealed significant activations linked to the CPT in the right supplementary motor cortex, midcingulate (bilateral) and the right anterior insular cortex. The brainstem-specific analysis showed significant activations in the dorsal medulla. Conclusion Changes in BOLD fMRI signal intensity in brainstem regions during a CPT can be detected, and show an increased response during a cold stress in healthy volunteers. https://www.selleckchem.com/products/fx-909.html Consequently, BOLD fMRI at 7T is a promising tool to explore and acquire new insights in the comprehension of neurogenic hypertension. Copyright © 2020 Hendriks-Balk, Megdiche, Pezzi, Reynaud, Da Costa, Bueti, Van De Ville and Wuerzner.Background With a decrease in heroin's purity and availability in the European drug market, Hungarian opioid dependent patients started to substitute heroin with novel psychoactive substances (NPS) and especially with synthetic cathinones. Goal This study aims to assess whether clients of opioid substitution treatment (OST) with and without a history of synthetic cathinone use during therapy differ in (1) the rate and type of experienced childhood trauma, (2) the way they cope with negative life events, (3) their motivation to change substance use behavior, (4) the rate of treatment retention. Methods A total of 198 clients of an outpatient centers (Nyírõ Gyula National Institute of Psychiatry and Addictions, Budapest) OST were asked to provide information about their general substance use experiences, including the consumption of NPS during treatment, their childhood traumatic experiences (Childhood Trauma Questionnaire), cognitive emotion regulation strategies (Cognitive Emotion Regulation Questionnaire), tn 0.05) and was associated with lower odds of being member of a latent class with less severe psychopathological profile (B = -0.9, OR = 0.4, p less then 0.05). Conclusion Synthetic cathinone use during treatment is associated with poorer treatment outcomes and might be characterized by more severe psychiatric symptoms and amotivation to change substance use among opioid dependent clients. Copyright © 2020 Kapitány-Fövény, Kiss, Farkas, Kuczora, Pataki, Horváth and Demetrovics.Resting-state functional connectivity (RSFC) has been generally assessed with functional magnetic resonance imaging (fMRI) thanks to its high spatial resolution. However, fMRI has several disadvantages such as high cost and low portability. In addition, fMRI may not be appropriate for people with metal or electronic implants in their bodies, with claustrophobia and who are pregnant. Diffuse optical tomography (DOT), a method of neuroimaging using functional near-infrared spectroscopy (fNIRS) to reconstruct three-dimensional brain activity images, offers a non-invasive alternative, because fNIRS as well as fMRI measures changes in deoxygenated hemoglobin concentrations and, in addition, fNIRS is free of above disadvantages. We recently proposed a hierarchical Bayesian (HB) DOT algorithm and verified its performance in terms of task-related brain responses. In this study, we attempted to evaluate the HB DOT in terms of estimating RSFC. In 20 healthy males (21-38 years old), 10 min of resting-state data was acquired with 3T MRI scanner or high-density NIRS on different days. The NIRS channels consisted of 96 long (29-mm) source-detector (SD) channels and 56 short (13-mm) SD channels, which covered bilateral frontal and parietal areas. There were one and two resting-state runs in the fMRI and fNIRS experiments, respectively. The reconstruction performances of our algorithm and the two currently prevailing algorithms for DOT were evaluated using fMRI signals as a reference. Compared with the currently prevailing algorithms, our HB algorithm showed better performances in both the similarity to fMRI data and inter-run reproducibility, in terms of estimating the RSFC. Copyright © 2020 Aihara, Shimokawa, Ogawa, Okada, Ishikawa, Inoue and Yamashita.Airway vagal hypertonia is closely related to the severity of asthma; however, the mechanisms of its genesis are unclear. This study aims to prove that asthmatic airway vagal hypertonia involves neuronal Cl- dyshomeostasis. The experimental airway allergy model was prepared with ovalbumin in male adult Sprague-Dawley rats. Plethysmography was used to evaluate airway vagal response to intracisternally injected γ-aminobutyric acid (GABA). Immunofluorescent staining and Western-blot assay were used to examine the expression of microglia-specific proteins, Na+-K+-2Cl- co-transporter 1 (NKCC1), K+-Cl- co-transporter 2 (KCC2) and brain-derived nerve growth factor (BDNF) in airway vagal centers. Pulmonary inflammatory changes were examined with hematoxylin and eosin staining of lung sections and ELISA assay of ovalbumin-specific IgE in bronchoalveolar lavage fluid (BALF). The results showed that histochemically, experimental airway allergy activated microglia, upregulated NKCC1, downregulated KCC2, and increased the content of BDNF in airway vagal centers. Functionally, experimental airway allergy augmented the excitatory airway vagal response to intracisternally injected GABA, which was attenuated by intracisternally pre-injected NKCC1 inhibitor bumetanide. All of the changes induced by experimental airway allergy were prevented or mitigated by chronic intracerebroventricular or intraperitoneal injection of minocycline, an inhibitor of microglia activation. These results demonstrate that experimental airway allergy augments the excitatory response of airway vagal centers to GABA, which might be the result of neuronal Cl- dyshomeostasis subsequent to microglia activation, increased BDNF release and altered expression of Cl- transporters. Cl- dyshomeostasis in airway vagal centers might contribute to the genesis of airway vagal hypertonia in asthma. Copyright © 2020 He, Chen, Zeng, Xia, Wang, Shen, Zhu, Chen and Wang.Object Excessive daytime sleepiness (EDS) is common in Parkinson disease (PD), but the neural basis of EDS in PD is unclear. We aim to analyze the neural activity changes in PD-related EDS. Methods In the present study, 38 PD patients and 19 healthy controls underwent clinical assessments and resting state functional magnetic resonance imaging (MRI) at 3T. Patients were further classified into PD patients with EDS (n = 17) and PD patients without EDS (n = 21), according to the Epworth Sleepiness Scale (ESS) cutoff score with greater than 10 or less than 3. We evaluated all patients using PD-related motor and non-motor clinical scales. An analysis of covariance and post hoc two-sample t-tests were performed to examine between-groups differences of the amplitude of low-frequency fluctuations (ALFF) and functional connectivity (FC). Results We found that, all PD-EDS subjects in our study were male. Compared with the control subjects, PD patients with EDS had decreased ALFF in the Pons and increased ALFF in the Frontal_Mid_Orb_L (p less then 0.
    9 years) were analyzed. Mean arterial BP increased from 83 ± 12 mm Hg to 87 ± 12 mm Hg (p = 0.0009) during the CPT. Whole-brain analysis revealed significant activations linked to the CPT in the right supplementary motor cortex, midcingulate (bilateral) and the right anterior insular cortex. The brainstem-specific analysis showed significant activations in the dorsal medulla. Conclusion Changes in BOLD fMRI signal intensity in brainstem regions during a CPT can be detected, and show an increased response during a cold stress in healthy volunteers. https://www.selleckchem.com/products/fx-909.html Consequently, BOLD fMRI at 7T is a promising tool to explore and acquire new insights in the comprehension of neurogenic hypertension. Copyright © 2020 Hendriks-Balk, Megdiche, Pezzi, Reynaud, Da Costa, Bueti, Van De Ville and Wuerzner.Background With a decrease in heroin's purity and availability in the European drug market, Hungarian opioid dependent patients started to substitute heroin with novel psychoactive substances (NPS) and especially with synthetic cathinones. Goal This study aims to assess whether clients of opioid substitution treatment (OST) with and without a history of synthetic cathinone use during therapy differ in (1) the rate and type of experienced childhood trauma, (2) the way they cope with negative life events, (3) their motivation to change substance use behavior, (4) the rate of treatment retention. Methods A total of 198 clients of an outpatient centers (Nyírõ Gyula National Institute of Psychiatry and Addictions, Budapest) OST were asked to provide information about their general substance use experiences, including the consumption of NPS during treatment, their childhood traumatic experiences (Childhood Trauma Questionnaire), cognitive emotion regulation strategies (Cognitive Emotion Regulation Questionnaire), tn 0.05) and was associated with lower odds of being member of a latent class with less severe psychopathological profile (B = -0.9, OR = 0.4, p less then 0.05). Conclusion Synthetic cathinone use during treatment is associated with poorer treatment outcomes and might be characterized by more severe psychiatric symptoms and amotivation to change substance use among opioid dependent clients. Copyright © 2020 Kapitány-Fövény, Kiss, Farkas, Kuczora, Pataki, Horváth and Demetrovics.Resting-state functional connectivity (RSFC) has been generally assessed with functional magnetic resonance imaging (fMRI) thanks to its high spatial resolution. However, fMRI has several disadvantages such as high cost and low portability. In addition, fMRI may not be appropriate for people with metal or electronic implants in their bodies, with claustrophobia and who are pregnant. Diffuse optical tomography (DOT), a method of neuroimaging using functional near-infrared spectroscopy (fNIRS) to reconstruct three-dimensional brain activity images, offers a non-invasive alternative, because fNIRS as well as fMRI measures changes in deoxygenated hemoglobin concentrations and, in addition, fNIRS is free of above disadvantages. We recently proposed a hierarchical Bayesian (HB) DOT algorithm and verified its performance in terms of task-related brain responses. In this study, we attempted to evaluate the HB DOT in terms of estimating RSFC. In 20 healthy males (21-38 years old), 10 min of resting-state data was acquired with 3T MRI scanner or high-density NIRS on different days. The NIRS channels consisted of 96 long (29-mm) source-detector (SD) channels and 56 short (13-mm) SD channels, which covered bilateral frontal and parietal areas. There were one and two resting-state runs in the fMRI and fNIRS experiments, respectively. The reconstruction performances of our algorithm and the two currently prevailing algorithms for DOT were evaluated using fMRI signals as a reference. Compared with the currently prevailing algorithms, our HB algorithm showed better performances in both the similarity to fMRI data and inter-run reproducibility, in terms of estimating the RSFC. Copyright © 2020 Aihara, Shimokawa, Ogawa, Okada, Ishikawa, Inoue and Yamashita.Airway vagal hypertonia is closely related to the severity of asthma; however, the mechanisms of its genesis are unclear. This study aims to prove that asthmatic airway vagal hypertonia involves neuronal Cl- dyshomeostasis. The experimental airway allergy model was prepared with ovalbumin in male adult Sprague-Dawley rats. Plethysmography was used to evaluate airway vagal response to intracisternally injected γ-aminobutyric acid (GABA). Immunofluorescent staining and Western-blot assay were used to examine the expression of microglia-specific proteins, Na+-K+-2Cl- co-transporter 1 (NKCC1), K+-Cl- co-transporter 2 (KCC2) and brain-derived nerve growth factor (BDNF) in airway vagal centers. Pulmonary inflammatory changes were examined with hematoxylin and eosin staining of lung sections and ELISA assay of ovalbumin-specific IgE in bronchoalveolar lavage fluid (BALF). The results showed that histochemically, experimental airway allergy activated microglia, upregulated NKCC1, downregulated KCC2, and increased the content of BDNF in airway vagal centers. Functionally, experimental airway allergy augmented the excitatory airway vagal response to intracisternally injected GABA, which was attenuated by intracisternally pre-injected NKCC1 inhibitor bumetanide. All of the changes induced by experimental airway allergy were prevented or mitigated by chronic intracerebroventricular or intraperitoneal injection of minocycline, an inhibitor of microglia activation. These results demonstrate that experimental airway allergy augments the excitatory response of airway vagal centers to GABA, which might be the result of neuronal Cl- dyshomeostasis subsequent to microglia activation, increased BDNF release and altered expression of Cl- transporters. Cl- dyshomeostasis in airway vagal centers might contribute to the genesis of airway vagal hypertonia in asthma. Copyright © 2020 He, Chen, Zeng, Xia, Wang, Shen, Zhu, Chen and Wang.Object Excessive daytime sleepiness (EDS) is common in Parkinson disease (PD), but the neural basis of EDS in PD is unclear. We aim to analyze the neural activity changes in PD-related EDS. Methods In the present study, 38 PD patients and 19 healthy controls underwent clinical assessments and resting state functional magnetic resonance imaging (MRI) at 3T. Patients were further classified into PD patients with EDS (n = 17) and PD patients without EDS (n = 21), according to the Epworth Sleepiness Scale (ESS) cutoff score with greater than 10 or less than 3. We evaluated all patients using PD-related motor and non-motor clinical scales. An analysis of covariance and post hoc two-sample t-tests were performed to examine between-groups differences of the amplitude of low-frequency fluctuations (ALFF) and functional connectivity (FC). Results We found that, all PD-EDS subjects in our study were male. Compared with the control subjects, PD patients with EDS had decreased ALFF in the Pons and increased ALFF in the Frontal_Mid_Orb_L (p less then 0.
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  • The amalgamation of the ORL Research Societies as a Specialty Group within ENT-UK to organise and run the national research agenda is likely to result in a more cohesive group with financial stability and a secure and stable environment. This article is protected by copyright. All rights reserved.Breast cancer is a common malignant tumor suffered predominantly by women worldwide, which results in serious levels of morbidity and mortality. To control the effects of the cancer, it is critically important to elucidate the pathophysiological processes by which it occurs and develops. Reports have demonstrated that long noncoding RNAs perform a critical role in the development and metastasis of cancers. The lncRNA TTN-AS1 is considered carcinogenic. Nevertheless, the importance and biological functions of TTN-AS1 in breast cancer require greater exploration. In the current paper, we observed that TTN-AS1 expression was significantly upregulated in breast cancer tissues/cells compared with those that are healthy. TTN-AS1 enhanced the proliferation, migration, invasion, and epithelial-mesenchymal transformation of breast cancer cells. Furthermore, a direct target of TTN-AS1, miR-139-5p was negatively regulated. In addition, zinc finger E-box binding homeobox 1 (ZEB1) is an important nuclear transcription factor, the expression of which is increased in multiple tumors. Here, we also found that ZEB1 is a target of miR-139-5p, of which TTN-AS1 could regulate the expression through competition with miR-139-5p. That is, TTN-AS1 promoted proliferation and invasion of breast cancer cells by interaction with the miR-139-5p/ZEB1 axis. In conclusion, the present study aimed to illustrate the significance of TTN-AS1 in breast cancer metastasis and contribute to potentially innovative strategies for its treatment. © 2020 Wiley Periodicals, Inc.Chronic lymphocytic leukemia (CLL), a severe problem all over the world and represents around 25% of all total leukemia cases, is generating the need for novel targets against CLL. Wnt signaling cascade regulates cell proliferation, differentiation, and cell death processes. Thus, any alteration of the Wnt signaling pathway protein cascade might develop into various types of cancers, either by upregulation or downregulation of the Wnt signaling pathway protein components. In addition, it is reported that activation of the Wnt signaling pathway is associated with the transcriptional activation of microRNAs (miRNAs) by binding to its promoter region, suggesting feedback regulation. Considering the protein regulatory functions of various miRNAs, they can be approached therapeutically as modulatory targets for protein components of the Wnt signaling pathway. https://www.selleckchem.com/products/e7766-diammonium-salt.html In this article, we have discussed the potential role of miRNAs in the regulation of Wnt signaling pathway proteins related to the pathogenesis of CLL via crosstalk between miRNAs and Wnt signaling pathway proteins. This might provide a clear insight into the Wnt protein regulatory function of various miRNAs and provide a better understanding of developing advanced and promising therapeutic approaches against CLL. © 2020 Wiley Periodicals, Inc.Incorporating heteroatoms in functional materials is an invaluable approach to modulate their properties, assuming a solid solution is formed. However, thorough understanding of key structural information on the resulting solid solution, such as the local environment of cations and vacancies, remains a challenge. Solid-state NMR (SSNMR) spectroscopy is a powerful structural characterization tool, very sensitive to the local environment. Due to the difficulty in signal acquisition and spectral interpretation, SSNMR spectroscopy is relatively less known to chemists and materials scientists. Herein, we present an introductory review to demonstrate how to use 89Y SSNMR spectroscopy to unravel the mystery of solid solutions. In general, 89Y chemical shift varies with different cation/vacancy arrangements in Y coordination spheres, providing ultrafine structural information in the atomic scale. As a case study and an extreme condition, the approach demonstrated in this review can be extended to other systems. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.A key component of research on human sentence processing is to characterize the processing difficulty associated with the comprehension of words in context. Models that explain and predict this difficulty can be broadly divided into two kinds, expectation-based and memory-based. In this work, we present a new model of incremental sentence processing difficulty that unifies and extends key features of both kinds of models. Our model, lossy-context surprisal, holds that the processing difficulty at a word in context is proportional to the surprisal of the word given a lossy memory representation of the context-that is, a memory representation that does not contain complete information about previous words. We show that this model provides an intuitive explanation for an outstanding puzzle involving interactions of memory and expectations language-dependent structural forgetting, where the effects of memory on sentence processing appear to be moderated by language statistics. Furthermore, we demonstrate that dependency locality effects, a signature prediction of memory-based theories, can be derived from lossy-context surprisal as a special case of a novel, more general principle called information locality. Copyright © 2020 The Authors. Cognitive Science published by Wiley Periodicals, Inc. on behalf of Cognitive Science Society (CSS).IMPORTANCE Atropine eyedrops are a promising treatment for slowing myopia progression in East Asian children. However, its effects on children in Australia, including those of non-Asian background, have not been well-studied. BACKGROUND The Western Australia Atropine for the Treatment of Myopia (WA-ATOM) study aims to determine the efficacy and long-term effects of low-dose atropine eyedrops in myopia control. This paper describes the study rationale, methodology, and participant baseline characteristics. DESIGN Single-centre, double-masked, randomised controlled trial. PARTICIPANTS Children (6-16 years) with spherical equivalent ≤ - 1.50D in each eye, astigmatism ≤1.50D, and myopia progression by ≥0.50D/year. METHODS Enrolled children were randomly assigned 21 to receive 0.01% atropine or placebo eyedrops. Participants are examined every six months during first three years of the study (2-year treatment phase followed by a 1-year washout phase), and then at a 5-year follow-up (two years after the end of the washout phase).
    The amalgamation of the ORL Research Societies as a Specialty Group within ENT-UK to organise and run the national research agenda is likely to result in a more cohesive group with financial stability and a secure and stable environment. This article is protected by copyright. All rights reserved.Breast cancer is a common malignant tumor suffered predominantly by women worldwide, which results in serious levels of morbidity and mortality. To control the effects of the cancer, it is critically important to elucidate the pathophysiological processes by which it occurs and develops. Reports have demonstrated that long noncoding RNAs perform a critical role in the development and metastasis of cancers. The lncRNA TTN-AS1 is considered carcinogenic. Nevertheless, the importance and biological functions of TTN-AS1 in breast cancer require greater exploration. In the current paper, we observed that TTN-AS1 expression was significantly upregulated in breast cancer tissues/cells compared with those that are healthy. TTN-AS1 enhanced the proliferation, migration, invasion, and epithelial-mesenchymal transformation of breast cancer cells. Furthermore, a direct target of TTN-AS1, miR-139-5p was negatively regulated. In addition, zinc finger E-box binding homeobox 1 (ZEB1) is an important nuclear transcription factor, the expression of which is increased in multiple tumors. Here, we also found that ZEB1 is a target of miR-139-5p, of which TTN-AS1 could regulate the expression through competition with miR-139-5p. That is, TTN-AS1 promoted proliferation and invasion of breast cancer cells by interaction with the miR-139-5p/ZEB1 axis. In conclusion, the present study aimed to illustrate the significance of TTN-AS1 in breast cancer metastasis and contribute to potentially innovative strategies for its treatment. © 2020 Wiley Periodicals, Inc.Chronic lymphocytic leukemia (CLL), a severe problem all over the world and represents around 25% of all total leukemia cases, is generating the need for novel targets against CLL. Wnt signaling cascade regulates cell proliferation, differentiation, and cell death processes. Thus, any alteration of the Wnt signaling pathway protein cascade might develop into various types of cancers, either by upregulation or downregulation of the Wnt signaling pathway protein components. In addition, it is reported that activation of the Wnt signaling pathway is associated with the transcriptional activation of microRNAs (miRNAs) by binding to its promoter region, suggesting feedback regulation. Considering the protein regulatory functions of various miRNAs, they can be approached therapeutically as modulatory targets for protein components of the Wnt signaling pathway. https://www.selleckchem.com/products/e7766-diammonium-salt.html In this article, we have discussed the potential role of miRNAs in the regulation of Wnt signaling pathway proteins related to the pathogenesis of CLL via crosstalk between miRNAs and Wnt signaling pathway proteins. This might provide a clear insight into the Wnt protein regulatory function of various miRNAs and provide a better understanding of developing advanced and promising therapeutic approaches against CLL. © 2020 Wiley Periodicals, Inc.Incorporating heteroatoms in functional materials is an invaluable approach to modulate their properties, assuming a solid solution is formed. However, thorough understanding of key structural information on the resulting solid solution, such as the local environment of cations and vacancies, remains a challenge. Solid-state NMR (SSNMR) spectroscopy is a powerful structural characterization tool, very sensitive to the local environment. Due to the difficulty in signal acquisition and spectral interpretation, SSNMR spectroscopy is relatively less known to chemists and materials scientists. Herein, we present an introductory review to demonstrate how to use 89Y SSNMR spectroscopy to unravel the mystery of solid solutions. In general, 89Y chemical shift varies with different cation/vacancy arrangements in Y coordination spheres, providing ultrafine structural information in the atomic scale. As a case study and an extreme condition, the approach demonstrated in this review can be extended to other systems. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.A key component of research on human sentence processing is to characterize the processing difficulty associated with the comprehension of words in context. Models that explain and predict this difficulty can be broadly divided into two kinds, expectation-based and memory-based. In this work, we present a new model of incremental sentence processing difficulty that unifies and extends key features of both kinds of models. Our model, lossy-context surprisal, holds that the processing difficulty at a word in context is proportional to the surprisal of the word given a lossy memory representation of the context-that is, a memory representation that does not contain complete information about previous words. We show that this model provides an intuitive explanation for an outstanding puzzle involving interactions of memory and expectations language-dependent structural forgetting, where the effects of memory on sentence processing appear to be moderated by language statistics. Furthermore, we demonstrate that dependency locality effects, a signature prediction of memory-based theories, can be derived from lossy-context surprisal as a special case of a novel, more general principle called information locality. Copyright © 2020 The Authors. Cognitive Science published by Wiley Periodicals, Inc. on behalf of Cognitive Science Society (CSS).IMPORTANCE Atropine eyedrops are a promising treatment for slowing myopia progression in East Asian children. However, its effects on children in Australia, including those of non-Asian background, have not been well-studied. BACKGROUND The Western Australia Atropine for the Treatment of Myopia (WA-ATOM) study aims to determine the efficacy and long-term effects of low-dose atropine eyedrops in myopia control. This paper describes the study rationale, methodology, and participant baseline characteristics. DESIGN Single-centre, double-masked, randomised controlled trial. PARTICIPANTS Children (6-16 years) with spherical equivalent ≤ - 1.50D in each eye, astigmatism ≤1.50D, and myopia progression by ≥0.50D/year. METHODS Enrolled children were randomly assigned 21 to receive 0.01% atropine or placebo eyedrops. Participants are examined every six months during first three years of the study (2-year treatment phase followed by a 1-year washout phase), and then at a 5-year follow-up (two years after the end of the washout phase).
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  • In non-habitual situations, cognitive control aligns actions with both short- and long-term goals. The capacity for cognitive control is tightly tied to the prefrontal cortex, whose expansion in humans relative to other species is thought to support our superior cognitive control. However, the posterolateral cerebellum has also expanded greatly relative to non-human primates and has an organizational structure that mirrors the prefrontal cortex. Nevertheless, cerebellar contributions to cognitive control are poorly understood. Here, we sought to explore whether a functional hierarchical processing framework, applied to the cerebellum, could elucidate cerebellar contributions to cognitive control. Using functional magnetic resonance imaging, we show that a gradient within the posterolateral cerebellum supports cognitive control with motor-adjacent cerebellar sub-regions supporting control of concrete, proximal actions and motor-distal, cerebellar sub-regions supporting abstract, future processing. This gradient was functionally hierarchical, with regions higher in the hierarchy influencing the relationship between regions lower in the hierarchy. This functional hierarchy provides the infrastructure by which context can inform current actions and prepare for future goals. Crucially, this mirrors the hierarchical organization of cognitive control within the prefrontal cortex. Based on these findings, we propose that the cerebellum contains within itself a parallel but separate hierarchical organization that, along with the prefrontal cortex, supports complex cognition. Path integration is a robust mechanism that many animals employ to return to specific locations, typically their homes, during navigation. This efficient navigational strategy has never been demonstrated in a fully aquatic animal, where sensory cues used for orientation may differ dramatically from those available above the water's surface. Here, we report that the mantis shrimp, Neogonodactylus oerstedii, uses path integration informed by a hierarchical reliance on the sun, overhead polarization patterns, and idiothetic (internal) orientation cues to return home when foraging, making them the first fully aquatic path-integrating animals yet discovered. We show that mantis shrimp rely on navigational strategies closely resembling those used by insect navigators, opening a new avenue for the investigation of the neural basis of navigation behaviors and the evolution of these strategies in arthropods and potentially other animals as well. VIDEO ABSTRACT. Published by Elsevier Inc.The plant hormone auxin serves as central regulator of growth and development. Auxin transporters in the plasma membrane are assumed to define tissue-level patterns of auxin distribution [1, 2]. However, auxin is small enough to diffuse through the plasmodesmata that connect neighboring cells [3], presenting an alternative pathway, whose contribution to auxin transport remained largely unexplored [4]. Here, photoactivation microscopy [5, 6] was used to measure the capacity for small-molecule diffusion in the epidermis of Arabidopsis thaliana leaves. In the elongated epidermis cells covering the midrib and petiole, the plasmodesmata-mediated cell-wall permeability was found to be several times higher in the longitudinal than in the transverse direction. The physiological relevance of this asymmetry was tested through quantification of the shade-avoidance response, which depends on auxin transport from the leaf tip to the petiole in the abaxial side of the leaf [7], with the hypothesis that directionality of diffusion supplements transporter-mediated auxin movement [8]. Triggering the response by auxin application at the tip led to stronger leaf movement in wild-type plants than in gsl8 mutants [9], which lack the callose synthase necessary to establish directionality. The results match the predictions of a mathematical model of auxin transport based on the permeabilities measured in wild-type and mutant plants. It is concluded that plasmodesmata permeability can be selectively modulated within a plant cell and that the conferred directionality in diffusion can influence the tissue-specific distribution patterns of small molecules, like auxin. Associations formed between plants and arbuscular mycorrhizal (AM) fungi are characterized by the bi-directional exchange of fungal-acquired soil nutrients for plant-fixed organic carbon compounds. Mycorrhizal-acquired nutrient assimilation by plants may be symmetrically linked to carbon (C) transfer from plant to fungus or governed by sink-source dynamics. Abiotic factors, including atmospheric CO2 concentration ([CO2]), can affect the relative cost of resources traded between mutualists, thereby influencing symbiotic function. Whether biotic factors, such as insect herbivores that represent external sinks for plant C, impact mycorrhizal function remains unstudied. By supplying 33P to an AM fungus (Rhizophagus irregularis) and 14CO2 to wheat, we tested the impact of increasing C sink strength (i.e., aphid herbivory) and increasing C source strength (i.e., elevated [CO2]) on resource exchange between mycorrhizal symbionts. Allocation of plant C to the AM fungus decreased dramatically following exposure to the bird cherry-oat aphid (Rhopalosiphum padi), with high [CO2] failing to alleviate the aphid-induced decline in plant C allocated to the AM fungus. Mycorrhizal-mediated uptake of 33P by plants was maintained regardless of aphid presence or elevated [CO2], meaning insect herbivory drove asymmetry in carbon for nutrient exchange between symbionts. Here, we provide direct evidence that external biotic C sinks can limit plant C allocation to an AM fungus without hindering mycorrhizal-acquired nutrient uptake. Our findings highlight the context dependency of resource exchange between plants and AM fungi and suggest biotic factors-individually and in combination with abiotic factors-should be considered as powerful regulators of symbiotic function. Crown All rights reserved.Evolutionary theory expects social, communicative species to eavesdrop most on other species' alarm calls [e.g., 1, 2] but also that solitary-living species benefit most from eavesdropping [3, 4]. Examples of solitary species responding to the alarm calls of other species, however, are limited and unconvincing [3-5]. The Swahili name for the red-billed oxpecker (Buphagus erythrorynchus) is Askari wa kifaru, the rhinos' guard [6]. Black rhino (Diceros bicornis) are a solitary-living, non-vocal species and are critically endangered through hunting. https://www.selleckchem.com/products/roc-325.html We searched Hluhluwe-iMfolozi Park, South Africa, for rhinoceros for 27 months with and without the aid of radio telemetry and conducted 86 experimental, unconcealed approaches to 11 rhino, without or with varying numbers of resident oxpecker. Oxpeckers enabled rhinos to evade detection by us in 40% to 50% of encounters. Alarm-calling by oxpeckers significantly improved the rate and distance that rhinos detected our approach from 23% to 100% and 27 ± 6 m to 61 ± 4 m, respectively.
    In non-habitual situations, cognitive control aligns actions with both short- and long-term goals. The capacity for cognitive control is tightly tied to the prefrontal cortex, whose expansion in humans relative to other species is thought to support our superior cognitive control. However, the posterolateral cerebellum has also expanded greatly relative to non-human primates and has an organizational structure that mirrors the prefrontal cortex. Nevertheless, cerebellar contributions to cognitive control are poorly understood. Here, we sought to explore whether a functional hierarchical processing framework, applied to the cerebellum, could elucidate cerebellar contributions to cognitive control. Using functional magnetic resonance imaging, we show that a gradient within the posterolateral cerebellum supports cognitive control with motor-adjacent cerebellar sub-regions supporting control of concrete, proximal actions and motor-distal, cerebellar sub-regions supporting abstract, future processing. This gradient was functionally hierarchical, with regions higher in the hierarchy influencing the relationship between regions lower in the hierarchy. This functional hierarchy provides the infrastructure by which context can inform current actions and prepare for future goals. Crucially, this mirrors the hierarchical organization of cognitive control within the prefrontal cortex. Based on these findings, we propose that the cerebellum contains within itself a parallel but separate hierarchical organization that, along with the prefrontal cortex, supports complex cognition. Path integration is a robust mechanism that many animals employ to return to specific locations, typically their homes, during navigation. This efficient navigational strategy has never been demonstrated in a fully aquatic animal, where sensory cues used for orientation may differ dramatically from those available above the water's surface. Here, we report that the mantis shrimp, Neogonodactylus oerstedii, uses path integration informed by a hierarchical reliance on the sun, overhead polarization patterns, and idiothetic (internal) orientation cues to return home when foraging, making them the first fully aquatic path-integrating animals yet discovered. We show that mantis shrimp rely on navigational strategies closely resembling those used by insect navigators, opening a new avenue for the investigation of the neural basis of navigation behaviors and the evolution of these strategies in arthropods and potentially other animals as well. VIDEO ABSTRACT. Published by Elsevier Inc.The plant hormone auxin serves as central regulator of growth and development. Auxin transporters in the plasma membrane are assumed to define tissue-level patterns of auxin distribution [1, 2]. However, auxin is small enough to diffuse through the plasmodesmata that connect neighboring cells [3], presenting an alternative pathway, whose contribution to auxin transport remained largely unexplored [4]. Here, photoactivation microscopy [5, 6] was used to measure the capacity for small-molecule diffusion in the epidermis of Arabidopsis thaliana leaves. In the elongated epidermis cells covering the midrib and petiole, the plasmodesmata-mediated cell-wall permeability was found to be several times higher in the longitudinal than in the transverse direction. The physiological relevance of this asymmetry was tested through quantification of the shade-avoidance response, which depends on auxin transport from the leaf tip to the petiole in the abaxial side of the leaf [7], with the hypothesis that directionality of diffusion supplements transporter-mediated auxin movement [8]. Triggering the response by auxin application at the tip led to stronger leaf movement in wild-type plants than in gsl8 mutants [9], which lack the callose synthase necessary to establish directionality. The results match the predictions of a mathematical model of auxin transport based on the permeabilities measured in wild-type and mutant plants. It is concluded that plasmodesmata permeability can be selectively modulated within a plant cell and that the conferred directionality in diffusion can influence the tissue-specific distribution patterns of small molecules, like auxin. Associations formed between plants and arbuscular mycorrhizal (AM) fungi are characterized by the bi-directional exchange of fungal-acquired soil nutrients for plant-fixed organic carbon compounds. Mycorrhizal-acquired nutrient assimilation by plants may be symmetrically linked to carbon (C) transfer from plant to fungus or governed by sink-source dynamics. Abiotic factors, including atmospheric CO2 concentration ([CO2]), can affect the relative cost of resources traded between mutualists, thereby influencing symbiotic function. Whether biotic factors, such as insect herbivores that represent external sinks for plant C, impact mycorrhizal function remains unstudied. By supplying 33P to an AM fungus (Rhizophagus irregularis) and 14CO2 to wheat, we tested the impact of increasing C sink strength (i.e., aphid herbivory) and increasing C source strength (i.e., elevated [CO2]) on resource exchange between mycorrhizal symbionts. Allocation of plant C to the AM fungus decreased dramatically following exposure to the bird cherry-oat aphid (Rhopalosiphum padi), with high [CO2] failing to alleviate the aphid-induced decline in plant C allocated to the AM fungus. Mycorrhizal-mediated uptake of 33P by plants was maintained regardless of aphid presence or elevated [CO2], meaning insect herbivory drove asymmetry in carbon for nutrient exchange between symbionts. Here, we provide direct evidence that external biotic C sinks can limit plant C allocation to an AM fungus without hindering mycorrhizal-acquired nutrient uptake. Our findings highlight the context dependency of resource exchange between plants and AM fungi and suggest biotic factors-individually and in combination with abiotic factors-should be considered as powerful regulators of symbiotic function. Crown All rights reserved.Evolutionary theory expects social, communicative species to eavesdrop most on other species' alarm calls [e.g., 1, 2] but also that solitary-living species benefit most from eavesdropping [3, 4]. Examples of solitary species responding to the alarm calls of other species, however, are limited and unconvincing [3-5]. The Swahili name for the red-billed oxpecker (Buphagus erythrorynchus) is Askari wa kifaru, the rhinos' guard [6]. Black rhino (Diceros bicornis) are a solitary-living, non-vocal species and are critically endangered through hunting. https://www.selleckchem.com/products/roc-325.html We searched Hluhluwe-iMfolozi Park, South Africa, for rhinoceros for 27 months with and without the aid of radio telemetry and conducted 86 experimental, unconcealed approaches to 11 rhino, without or with varying numbers of resident oxpecker. Oxpeckers enabled rhinos to evade detection by us in 40% to 50% of encounters. Alarm-calling by oxpeckers significantly improved the rate and distance that rhinos detected our approach from 23% to 100% and 27 ± 6 m to 61 ± 4 m, respectively.
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  • Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).Water-in-salt (WIS) electrolytes provide a promising path toward aqueous battery systems with enlarged operating voltage windows for better safety and environmental sustainability. In this work, a new electrode couple, LiV3O8-LiMn2O4, for aqueous Li-ion batteries is investigated to understand the mechanism by which the WIS electrolyte improves the cycling stability at an extended voltage window. Operando synchrotron transmission x-ray microscopy on the LiMn2O4 cathode reveals that the WIS electrolyte suppresses the mechanical damage to the electrode network and dissolution of the electrode particles, in addition to delaying the water decomposition process. Because the viscosity of WIS is notably higher, the reaction heterogeneity of the electrodes is quantified with x-ray absorption spectroscopic imaging, visualizing the kinetic limitations of the WIS electrolyte. This work furthers the mechanistic understanding of electrode-WIS electrolyte interactions and paves the way to explore the strategy to mitigate their possible kinetic limitations in three-dimensional architectures. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. https://www.selleckchem.com/products/scutellarin.html No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).The gliding bacterium Flavobacterium johnsoniae is known to have an adhesin, SprB, that moves along the cell surface on a spiral track. Following viscous shear, cells can be tethered by the addition of an anti-SprB antibody, causing spinning at 3 Hz. Labeling the type 9 secretion system (T9SS) with a YFP fusion of GldL showed a yellow fluorescent spot near the rotation axis, indicating that the motor driving the motion is associated with the T9SS. The distance between the rotation axis and the track (90 nm) was determined after adding a Cy3 label for SprB. A rotary motor spinning a pinion of radius 90 nm at 3 Hz would cause a spot on its periphery to move at 1.5 μm/s, the gliding speed. We suggest the pinion drives a flexible tread that carries SprB along a track fixed to the cell surface. Cells glide when this adhesin adheres to the solid substratum. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).Hexagonal boron nitride (hBN) is an insulating two-dimensional (2D) material with a large bandgap. Although known for its interfacing with other 2D materials and structural similarities to graphene, the potential use of hBN in 2D electronics is limited by its insulating nature. Here, we report atomically sharp twin boundaries at AA'/AB stacking boundaries in chemical vapor deposition-synthesized few-layer hBN. We find that the twin boundary is composed of a 6'6' configuration, showing conducting feature with a zero bandgap. Furthermore, the formation mechanism of the atomically sharp twin boundaries is suggested by an analogy with stacking combinations of AA'/AB based on the observations of extended Klein edges at the layer boundaries of AB-stacked hBN. The atomically sharp AA'/AB stacking boundary is promising as an ultimate 1D electron channel embedded in insulating pristine hBN. This study will provide insights into the fabrication of single-hBN electronic devices. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).When self-renewing pluripotent cells receive a differentiation signal, ongoing cell duplication needs to be coordinated with entry into a differentiation program. Accordingly, transcriptional activation of lineage specifier genes and cell differentiation is confined to the G1 phase of the cell cycle by unknown mechanisms. We found that Polycomb repressive complex 2 (PRC2) subunits are differentially recruited to lineage specifier gene promoters across cell cycle in mouse embryonic stem cells (mESCs). Jarid2 and the catalytic subunit Ezh2 are markedly accumulated at target promoters during S and G2 phases, while the transcriptionally activating subunits EPOP and EloB are enriched during G1 phase. Fluctuations in the recruitment of PRC2 subunits promote changes in RNA synthesis and RNA polymerase II binding that are compromised in Jarid2 -/- mESCs. Overall, we show that differential recruitment of PRC2 subunits across cell cycle enables the establishment of a chromatin state that facilitates the induction of cell differentiation in G1 phase. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).The contamination of indoor nonsmoking environments with thirdhand smoke (THS) is an important, poorly understood public health concern. Real-time THS off-gassing from smokers into a nonsmoking movie theater was observed with online and offline high-resolution mass spectrometry. Prominent emission events of THS tracers (e.g., 2,5-dimethylfuran, 2-methylfuran, and acetonitrile) and other tobacco-related volatile organic compounds (VOCs) coincided with the arrival of certain moviegoers and left residual contamination. These VOC emission events exposed occupants to the equivalent of 1 to 10 cigarettes of secondhand smoke, including multiple hazardous air pollutants (e.g., benzene and formaldehyde) at parts-per-billion concentrations. Nicotine and related intermediate-volatility nitrogen-containing compounds, which vaporized from clothes/bodies and recondensed onto aerosol, comprised 34% of observed functionalized organic aerosol abundance. Exposure to THS VOC emission events will be considerably enhanced in poorly ventilated or smaller spaces in contrast with a large, well-ventilated theater-amplifying concentrations and potential impacts on health and indoor chemistry.
    Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).Water-in-salt (WIS) electrolytes provide a promising path toward aqueous battery systems with enlarged operating voltage windows for better safety and environmental sustainability. In this work, a new electrode couple, LiV3O8-LiMn2O4, for aqueous Li-ion batteries is investigated to understand the mechanism by which the WIS electrolyte improves the cycling stability at an extended voltage window. Operando synchrotron transmission x-ray microscopy on the LiMn2O4 cathode reveals that the WIS electrolyte suppresses the mechanical damage to the electrode network and dissolution of the electrode particles, in addition to delaying the water decomposition process. Because the viscosity of WIS is notably higher, the reaction heterogeneity of the electrodes is quantified with x-ray absorption spectroscopic imaging, visualizing the kinetic limitations of the WIS electrolyte. This work furthers the mechanistic understanding of electrode-WIS electrolyte interactions and paves the way to explore the strategy to mitigate their possible kinetic limitations in three-dimensional architectures. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. https://www.selleckchem.com/products/scutellarin.html No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).The gliding bacterium Flavobacterium johnsoniae is known to have an adhesin, SprB, that moves along the cell surface on a spiral track. Following viscous shear, cells can be tethered by the addition of an anti-SprB antibody, causing spinning at 3 Hz. Labeling the type 9 secretion system (T9SS) with a YFP fusion of GldL showed a yellow fluorescent spot near the rotation axis, indicating that the motor driving the motion is associated with the T9SS. The distance between the rotation axis and the track (90 nm) was determined after adding a Cy3 label for SprB. A rotary motor spinning a pinion of radius 90 nm at 3 Hz would cause a spot on its periphery to move at 1.5 μm/s, the gliding speed. We suggest the pinion drives a flexible tread that carries SprB along a track fixed to the cell surface. Cells glide when this adhesin adheres to the solid substratum. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).Hexagonal boron nitride (hBN) is an insulating two-dimensional (2D) material with a large bandgap. Although known for its interfacing with other 2D materials and structural similarities to graphene, the potential use of hBN in 2D electronics is limited by its insulating nature. Here, we report atomically sharp twin boundaries at AA'/AB stacking boundaries in chemical vapor deposition-synthesized few-layer hBN. We find that the twin boundary is composed of a 6'6' configuration, showing conducting feature with a zero bandgap. Furthermore, the formation mechanism of the atomically sharp twin boundaries is suggested by an analogy with stacking combinations of AA'/AB based on the observations of extended Klein edges at the layer boundaries of AB-stacked hBN. The atomically sharp AA'/AB stacking boundary is promising as an ultimate 1D electron channel embedded in insulating pristine hBN. This study will provide insights into the fabrication of single-hBN electronic devices. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).When self-renewing pluripotent cells receive a differentiation signal, ongoing cell duplication needs to be coordinated with entry into a differentiation program. Accordingly, transcriptional activation of lineage specifier genes and cell differentiation is confined to the G1 phase of the cell cycle by unknown mechanisms. We found that Polycomb repressive complex 2 (PRC2) subunits are differentially recruited to lineage specifier gene promoters across cell cycle in mouse embryonic stem cells (mESCs). Jarid2 and the catalytic subunit Ezh2 are markedly accumulated at target promoters during S and G2 phases, while the transcriptionally activating subunits EPOP and EloB are enriched during G1 phase. Fluctuations in the recruitment of PRC2 subunits promote changes in RNA synthesis and RNA polymerase II binding that are compromised in Jarid2 -/- mESCs. Overall, we show that differential recruitment of PRC2 subunits across cell cycle enables the establishment of a chromatin state that facilitates the induction of cell differentiation in G1 phase. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).The contamination of indoor nonsmoking environments with thirdhand smoke (THS) is an important, poorly understood public health concern. Real-time THS off-gassing from smokers into a nonsmoking movie theater was observed with online and offline high-resolution mass spectrometry. Prominent emission events of THS tracers (e.g., 2,5-dimethylfuran, 2-methylfuran, and acetonitrile) and other tobacco-related volatile organic compounds (VOCs) coincided with the arrival of certain moviegoers and left residual contamination. These VOC emission events exposed occupants to the equivalent of 1 to 10 cigarettes of secondhand smoke, including multiple hazardous air pollutants (e.g., benzene and formaldehyde) at parts-per-billion concentrations. Nicotine and related intermediate-volatility nitrogen-containing compounds, which vaporized from clothes/bodies and recondensed onto aerosol, comprised 34% of observed functionalized organic aerosol abundance. Exposure to THS VOC emission events will be considerably enhanced in poorly ventilated or smaller spaces in contrast with a large, well-ventilated theater-amplifying concentrations and potential impacts on health and indoor chemistry.
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  • Interestingly, the activity of 9-HODEs was less than that of other regio-isomers, and 9-(E,E)-HODE tended to decrease PPARγ-target gene expression during the maturation of 3T3-L1 cells. In addition, 10- and 12-(Z,E)-HODEs, which we previously proposed as biomarkers for early-stage diabetes, exerted PPARγ agonist activity. These results indicate that all HODE isomers have PPARγ-binding affinity; however, they have different PPARγ agonist activity. Our findings may help to understand the biological function of lipid peroxidation products. Copyright 2020 The Author(s).The N6-methyladenosine modification at position 43 (m6A43) of U6 snRNA is catalyzed by METTL16, and is important for the 5'-splice site recognition by U6 snRNA during pre-mRNA splicing. Human METTL16 consists of the N-terminal methyltransferase domain (MTD) and the C-terminal vertebrate conserved region (VCR). While the MTD has an intrinsic property to recognize a specific sequence in the distinct structural context of RNA, the VCR functions have remained uncharacterized. Here, we present structural and functional analyses of the human METTL16 VCR. The VCR increases the affinity of METTL16 toward U6 snRNA, and the conserved basic region in VCR is important for the METTL16-U6 snRNA interaction. The VCR structure is topologically homologous to the C-terminal RNA binding domain, KA1, in U6 snRNA-specific terminal uridylyl transferase 1 (TUT1). A chimera of the N-terminal MTD of METTL16 and the C-terminal KA1 of TUT1 methylated U6 snRNA more efficiently than the MTD, indicating the functional conservation of the VCR and KA1 for U6 snRNA biogenesis. The VCR interacts with the internal stem-loop (ISL) within U6 snRNA, and this interaction would induce the conformational rearrangement of the A43-containing region of U6 snRNA, thereby modifying the RNA structure to become suitable for productive catalysis by the MTD. Therefore, the MTD and VCR in METTL16 cooperatively facilitate the m6A43 U6 snRNA modification. © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.Translation fidelity relies essentially on the ability of ribosomes to accurately recognize triplet interactions between codons on mRNAs and anticodons of tRNAs. To determine the codon-anticodon pairs that are efficiently accepted by the eukaryotic ribosome, we took advantage of the IRES from the intergenic region (IGR) of the Cricket Paralysis Virus. It contains an essential pseudoknot PKI that structurally and functionally mimics a codon-anticodon helix. We screened the entire set of 4096 possible combinations using ultrahigh-throughput screenings combining coupled transcription/translation and droplet-based microfluidics. Only 97 combinations are efficiently accepted and accommodated for translocation and further elongation 38 combinations involve cognate recognition with Watson-Crick pairs and 59 involve near-cognate recognition pairs with at least one mismatch. More than half of the near-cognate combinations (36/59) contain a G at the first position of the anticodon (numbered 34 of tRNA). G34-containing tRNAs decoding 4-codon boxes are almost absent from eukaryotic genomes in contrast to bacterial genomes. We reconstructed these missing tRNAs and could demonstrate that these tRNAs are toxic to cells due to their miscoding capacity in eukaryotic translation systems. We also show that the nature of the purine at position 34 is correlated with the nucleotides present at 32 and 38. © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.Osteosarcoma (OS) is a malignant tumor commonly observed in children and adolescents. Developmentally regulated GTP-binding protein (DRG) 1 plays an important role in embryonic development; aberrantly expressed DRG1 has been associated with pathological processes in cancer. The present study aimed to explore the role of DRG1 in OS and the mechanisms underlying DRG1 overexpression in OS. Clinical studies were performed to evaluate Drg1 expression in OS tissues and to identify a correlation between Drg1 expression and the clinicopathological features in patients with OS. Drg1 was knocked down in OS cells to determine its effects on cell viability, cell cycle distribution, apoptosis, migration, invasion, and colony formation rate. METTL3 and ELAVL1 were also silenced to determine their effects on the levels of N6-methyladenosine (m6A), RNA stability, and Drg1 expression. Higher levels of Drg1 mRNA and protein were observed in OS tissues than those in paracancerous tissues. High expression of DRG1 was associated with large tumor size and advanced clinical stages in OS. https://www.selleckchem.com/products/roc-325.html Silencing of Drg1 resulted in decreased viability and inhibition of the migration and colony formation abilities of OS cells; it also resulted in cell cycle arrest in the G2/M stage and induced apoptosis. Knockdown of METTL3 led to decreased m6A and Drg1 mRNA levels. ELAVL1 knockdown impaired the stability of DRG1 mRNA, thereby reducing both the mRNA and protein levels of DRG1. In all, DRG1 exerted tumorigenic effects in OS, and the up-regulation of DRG1 in OS was induced by METTL3 and ELAVL1 in an m6A-dependent manner. © 2020 The Author(s).Vaccinia-related kinase 1 (VRK1) is a chromatin-associated Ser-Thr kinase that regulates numerous down-stream factors including DNA repair as well as stress factors c-Jun and p53. Both c-Jun and p53 are phosphorylated at Ser63 and Thr18, respectively, in response to low glucose (40 mg/dL of medium) but not high glucose (140 mg/dL of medium) in human hepatoma-derived Huh-7 cells. Here, we have determined the molecular mechanism by which VRK1 phosphorylates these residues in response to glucose in Huh-7 cells. Human VRK1 auto-phosphorylates Ser376 and Thr386 in in vitro kinase assays.  In Huh-7 cells, this auto-phosphorylation activity is regulated by glucose signaling; Thr386 is auto-phosphorylated only in low glucose medium, while Ser376 is not phosphorylated in either medium.  A correlation of this low glucose response phosphorylation of Thr386 with the phosphorylation of c-Jun and p53 suggests that VRK1 phosphorylated at Thr386 catalyzes this phosphorylation. In fact, VRK1 knock down by siRNA decreases and over-expression of VRK1 T386D increases phosphorylated c-Jun and p53 in Huh-7 cells.
    Interestingly, the activity of 9-HODEs was less than that of other regio-isomers, and 9-(E,E)-HODE tended to decrease PPARγ-target gene expression during the maturation of 3T3-L1 cells. In addition, 10- and 12-(Z,E)-HODEs, which we previously proposed as biomarkers for early-stage diabetes, exerted PPARγ agonist activity. These results indicate that all HODE isomers have PPARγ-binding affinity; however, they have different PPARγ agonist activity. Our findings may help to understand the biological function of lipid peroxidation products. Copyright 2020 The Author(s).The N6-methyladenosine modification at position 43 (m6A43) of U6 snRNA is catalyzed by METTL16, and is important for the 5'-splice site recognition by U6 snRNA during pre-mRNA splicing. Human METTL16 consists of the N-terminal methyltransferase domain (MTD) and the C-terminal vertebrate conserved region (VCR). While the MTD has an intrinsic property to recognize a specific sequence in the distinct structural context of RNA, the VCR functions have remained uncharacterized. Here, we present structural and functional analyses of the human METTL16 VCR. The VCR increases the affinity of METTL16 toward U6 snRNA, and the conserved basic region in VCR is important for the METTL16-U6 snRNA interaction. The VCR structure is topologically homologous to the C-terminal RNA binding domain, KA1, in U6 snRNA-specific terminal uridylyl transferase 1 (TUT1). A chimera of the N-terminal MTD of METTL16 and the C-terminal KA1 of TUT1 methylated U6 snRNA more efficiently than the MTD, indicating the functional conservation of the VCR and KA1 for U6 snRNA biogenesis. The VCR interacts with the internal stem-loop (ISL) within U6 snRNA, and this interaction would induce the conformational rearrangement of the A43-containing region of U6 snRNA, thereby modifying the RNA structure to become suitable for productive catalysis by the MTD. Therefore, the MTD and VCR in METTL16 cooperatively facilitate the m6A43 U6 snRNA modification. © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.Translation fidelity relies essentially on the ability of ribosomes to accurately recognize triplet interactions between codons on mRNAs and anticodons of tRNAs. To determine the codon-anticodon pairs that are efficiently accepted by the eukaryotic ribosome, we took advantage of the IRES from the intergenic region (IGR) of the Cricket Paralysis Virus. It contains an essential pseudoknot PKI that structurally and functionally mimics a codon-anticodon helix. We screened the entire set of 4096 possible combinations using ultrahigh-throughput screenings combining coupled transcription/translation and droplet-based microfluidics. Only 97 combinations are efficiently accepted and accommodated for translocation and further elongation 38 combinations involve cognate recognition with Watson-Crick pairs and 59 involve near-cognate recognition pairs with at least one mismatch. More than half of the near-cognate combinations (36/59) contain a G at the first position of the anticodon (numbered 34 of tRNA). G34-containing tRNAs decoding 4-codon boxes are almost absent from eukaryotic genomes in contrast to bacterial genomes. We reconstructed these missing tRNAs and could demonstrate that these tRNAs are toxic to cells due to their miscoding capacity in eukaryotic translation systems. We also show that the nature of the purine at position 34 is correlated with the nucleotides present at 32 and 38. © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.Osteosarcoma (OS) is a malignant tumor commonly observed in children and adolescents. Developmentally regulated GTP-binding protein (DRG) 1 plays an important role in embryonic development; aberrantly expressed DRG1 has been associated with pathological processes in cancer. The present study aimed to explore the role of DRG1 in OS and the mechanisms underlying DRG1 overexpression in OS. Clinical studies were performed to evaluate Drg1 expression in OS tissues and to identify a correlation between Drg1 expression and the clinicopathological features in patients with OS. Drg1 was knocked down in OS cells to determine its effects on cell viability, cell cycle distribution, apoptosis, migration, invasion, and colony formation rate. METTL3 and ELAVL1 were also silenced to determine their effects on the levels of N6-methyladenosine (m6A), RNA stability, and Drg1 expression. Higher levels of Drg1 mRNA and protein were observed in OS tissues than those in paracancerous tissues. High expression of DRG1 was associated with large tumor size and advanced clinical stages in OS. https://www.selleckchem.com/products/roc-325.html Silencing of Drg1 resulted in decreased viability and inhibition of the migration and colony formation abilities of OS cells; it also resulted in cell cycle arrest in the G2/M stage and induced apoptosis. Knockdown of METTL3 led to decreased m6A and Drg1 mRNA levels. ELAVL1 knockdown impaired the stability of DRG1 mRNA, thereby reducing both the mRNA and protein levels of DRG1. In all, DRG1 exerted tumorigenic effects in OS, and the up-regulation of DRG1 in OS was induced by METTL3 and ELAVL1 in an m6A-dependent manner. © 2020 The Author(s).Vaccinia-related kinase 1 (VRK1) is a chromatin-associated Ser-Thr kinase that regulates numerous down-stream factors including DNA repair as well as stress factors c-Jun and p53. Both c-Jun and p53 are phosphorylated at Ser63 and Thr18, respectively, in response to low glucose (40 mg/dL of medium) but not high glucose (140 mg/dL of medium) in human hepatoma-derived Huh-7 cells. Here, we have determined the molecular mechanism by which VRK1 phosphorylates these residues in response to glucose in Huh-7 cells. Human VRK1 auto-phosphorylates Ser376 and Thr386 in in vitro kinase assays.  In Huh-7 cells, this auto-phosphorylation activity is regulated by glucose signaling; Thr386 is auto-phosphorylated only in low glucose medium, while Ser376 is not phosphorylated in either medium.  A correlation of this low glucose response phosphorylation of Thr386 with the phosphorylation of c-Jun and p53 suggests that VRK1 phosphorylated at Thr386 catalyzes this phosphorylation. In fact, VRK1 knock down by siRNA decreases and over-expression of VRK1 T386D increases phosphorylated c-Jun and p53 in Huh-7 cells.
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  • Overall performance of the dual-channel approach (kappa 0.71; 4-class accuracy 81.3%) significantly outperformed individual oximetry (kappa 0.61; 4-class accuracy 75.0%) and airflow (kappa 0.42; 4-class accuracy 61.5%). According to our findings, oximetry alone was able to reach notably high accuracy, particularly to confirm severe cases of the disease. Nevertheless, oximetry and airflow showed high complementarity leading to a remarkable performance increase compared to single-channel approaches. Consequently, their joint analysis via machine learning enables accurate abbreviated screening of OSA at home.Heart transplantation remains the definitive therapy of end-stage heart failure. Ischemia-reperfusion injury occurring during transplantation is a primary determinant of long-term outcome of heart transplantation and primary graft insufficiency. Modification of the nitric oxide/soluble guanylate cyclase/cyclic guanosine monophosphate signaling pathway appears to be one of the most promising among the pharmacological interventional options. We aimed at characterizing the cardio-protective effects of the soluble guanylate cyclase stimulator riociguat in a rat model of heterotopic heart transplantation. Donor Lewis rats were treated orally with either riociguat or placebo for two days (n = 9) in each transplanted group and (n = 7) in donor groups. Following explantation, hearts were heterotopically transplanted. After one hour reperfusion, left ventricular pressure-volume relations and coronary blood flow were recorded. https://www.selleckchem.com/products/trastuzumab-emtansine-t-dm1-.html Molecular biological measurements and histological examination were also completed. Left ventricular contractility (systolic pressure 117 ± 13 vs. 48 ± 5 mmHg, p  less then  0.001; dP/dtmax 2963 ± 221 vs. 1653 ± 159 mmHg/s, p  less then  0.001), active relaxation (dP/dtmin -2014 ± 305 vs. -1063 ± 177 mmHg/s, p = 0.02; all at 120 µl of left ventricular volume), and alteration of coronary blood flow standardized to heart weight (2.55 ± 0.32 vs. 1.67 ± 0.22 ml/min/g, p = 0.03) were markedly increased following preconditioning with riociguat. Myocardial apoptosis markers were also significantly reduced in the riociguat pretreated group as well as the antioxidant markers were elevated. Pharmacological preconditioning with riociguat decreases ischemia-reperfusion injury and improves donor organ function in our animal model of heart transplantation. Therefore, riociguat might be a potential cardioprotective agent.The relationship between alcohol consumption and sleep disturbance is complex. The association of alcohol dependence with insomnia is likely to be bidirectional in nature. Alcohol use is common among older people in many societies and the prevalence of insomnia tends to increase with age, therefore this group warrants particular consideration. We explored the cross sectional and long term (30 years) associations between alcohol drinking (volume and hazardous drinking) and sleep duration and insomnia in a general population study of older adults (6,117 male and female civil servants followed for 30 years). For men, drinking more than 21 units (approximately 168 grams) of alcohol per week, compared with not drinking, was associated with waking several times a night (odds ratio 1.30, confidence intervals 1.02-1.66). Men who maintained a heavy volume of drinking over the three decades of observation, or who had an unstable consumption pattern, tended to have worse sleep profiles in terms of waking tired and waking several times. Sustained male hazardous drinking (as measured by the AUDIT-C scale) was also associated with worse sleep profiles. Findings for women were not so clear. In this population based setting, drinking high volumes of alcohol may contribute to the prevalence of sleep problems in older age, particularly for men. People in this age group should be discouraged from using alcohol as a sleep aid.Although a meta-analysis previously suggested a positive relationship between diabetes and intraocular pressure (IOP), the interrelationships among diabetes, IOP, and other ocular biometric parameters remain unclear. The present study investigated the relationships of diabetes, haemoglobin A1c (HbA1c), and serum glucose with IOP and ocular hypertension (IOP > 21 mmHg) in non-glaucomatous Japanese adults living in Chikusei City. Diabetes was defined as a self-reported history of diabetes, the use of antidiabetic medication, or HbA1c levels ≥6.5%. Among 6,786 enrolled participants aged 40 years and above, 734 were classified as diabetic (10.8%). After adjusting for several confounders, the IOP values were significantly higher in participants with diabetes than in those without diabetes (14.4 ± 0.1 vs. 13.9 ± 0.1 mmHg, P  less then  0.001) and were also significantly increased in those with elevated HbA1c and serum glucose levels (both P  less then  0.001). Moreover, diabetes was significantly related to ocular hypertension (multivariable-adjusted odds ratio, 1.75; 95% confidence interval, 1.09-2.81; P  less then  0.05). The positive influence of diabetes with ocular hypertension was consistent even after adjustment for central corneal thickness. In conclusion, diabetes, elevated HbA1c, and increased serum glucose are significant contributing factors for elevated IOP.Proton irradiation is often used as a proxy for neutron irradiation but the irradiated layer is typically less then 50 μm deep; this presents a problem when trying to obtain mechanical test data as a function of irradiation level. Two novel methodologies have been developed to record stress-strain curves for thin proton-irradiated surface layers of SA-508-4N ferritic steel. In the first case, in-situ loading experiments are carried out using a combination of X-ray diffraction and digital image correlation on the near surface region in order to measure stress and strain, thereby eliminating the influence of the non-irradiated volume. The second approach is to manufacture small-scale tensile specimens containing only the proton irradiated volume but approaching the smallest representative volume of the material. This is achieved by high-speed focused ion beam (FIB) milling though the application of a Xe+ Plasma-FIB (PFIB). It is demonstrated that both techniques are capable of recording the early stage of uniaxial flow behaviour of the irradiated material with sufficient accuracy providing a measure of irradiation-induced shift of yield strength, strain hardening and tensile strength.
    Overall performance of the dual-channel approach (kappa 0.71; 4-class accuracy 81.3%) significantly outperformed individual oximetry (kappa 0.61; 4-class accuracy 75.0%) and airflow (kappa 0.42; 4-class accuracy 61.5%). According to our findings, oximetry alone was able to reach notably high accuracy, particularly to confirm severe cases of the disease. Nevertheless, oximetry and airflow showed high complementarity leading to a remarkable performance increase compared to single-channel approaches. Consequently, their joint analysis via machine learning enables accurate abbreviated screening of OSA at home.Heart transplantation remains the definitive therapy of end-stage heart failure. Ischemia-reperfusion injury occurring during transplantation is a primary determinant of long-term outcome of heart transplantation and primary graft insufficiency. Modification of the nitric oxide/soluble guanylate cyclase/cyclic guanosine monophosphate signaling pathway appears to be one of the most promising among the pharmacological interventional options. We aimed at characterizing the cardio-protective effects of the soluble guanylate cyclase stimulator riociguat in a rat model of heterotopic heart transplantation. Donor Lewis rats were treated orally with either riociguat or placebo for two days (n = 9) in each transplanted group and (n = 7) in donor groups. Following explantation, hearts were heterotopically transplanted. After one hour reperfusion, left ventricular pressure-volume relations and coronary blood flow were recorded. https://www.selleckchem.com/products/trastuzumab-emtansine-t-dm1-.html Molecular biological measurements and histological examination were also completed. Left ventricular contractility (systolic pressure 117 ± 13 vs. 48 ± 5 mmHg, p  less then  0.001; dP/dtmax 2963 ± 221 vs. 1653 ± 159 mmHg/s, p  less then  0.001), active relaxation (dP/dtmin -2014 ± 305 vs. -1063 ± 177 mmHg/s, p = 0.02; all at 120 µl of left ventricular volume), and alteration of coronary blood flow standardized to heart weight (2.55 ± 0.32 vs. 1.67 ± 0.22 ml/min/g, p = 0.03) were markedly increased following preconditioning with riociguat. Myocardial apoptosis markers were also significantly reduced in the riociguat pretreated group as well as the antioxidant markers were elevated. Pharmacological preconditioning with riociguat decreases ischemia-reperfusion injury and improves donor organ function in our animal model of heart transplantation. Therefore, riociguat might be a potential cardioprotective agent.The relationship between alcohol consumption and sleep disturbance is complex. The association of alcohol dependence with insomnia is likely to be bidirectional in nature. Alcohol use is common among older people in many societies and the prevalence of insomnia tends to increase with age, therefore this group warrants particular consideration. We explored the cross sectional and long term (30 years) associations between alcohol drinking (volume and hazardous drinking) and sleep duration and insomnia in a general population study of older adults (6,117 male and female civil servants followed for 30 years). For men, drinking more than 21 units (approximately 168 grams) of alcohol per week, compared with not drinking, was associated with waking several times a night (odds ratio 1.30, confidence intervals 1.02-1.66). Men who maintained a heavy volume of drinking over the three decades of observation, or who had an unstable consumption pattern, tended to have worse sleep profiles in terms of waking tired and waking several times. Sustained male hazardous drinking (as measured by the AUDIT-C scale) was also associated with worse sleep profiles. Findings for women were not so clear. In this population based setting, drinking high volumes of alcohol may contribute to the prevalence of sleep problems in older age, particularly for men. People in this age group should be discouraged from using alcohol as a sleep aid.Although a meta-analysis previously suggested a positive relationship between diabetes and intraocular pressure (IOP), the interrelationships among diabetes, IOP, and other ocular biometric parameters remain unclear. The present study investigated the relationships of diabetes, haemoglobin A1c (HbA1c), and serum glucose with IOP and ocular hypertension (IOP > 21 mmHg) in non-glaucomatous Japanese adults living in Chikusei City. Diabetes was defined as a self-reported history of diabetes, the use of antidiabetic medication, or HbA1c levels ≥6.5%. Among 6,786 enrolled participants aged 40 years and above, 734 were classified as diabetic (10.8%). After adjusting for several confounders, the IOP values were significantly higher in participants with diabetes than in those without diabetes (14.4 ± 0.1 vs. 13.9 ± 0.1 mmHg, P  less then  0.001) and were also significantly increased in those with elevated HbA1c and serum glucose levels (both P  less then  0.001). Moreover, diabetes was significantly related to ocular hypertension (multivariable-adjusted odds ratio, 1.75; 95% confidence interval, 1.09-2.81; P  less then  0.05). The positive influence of diabetes with ocular hypertension was consistent even after adjustment for central corneal thickness. In conclusion, diabetes, elevated HbA1c, and increased serum glucose are significant contributing factors for elevated IOP.Proton irradiation is often used as a proxy for neutron irradiation but the irradiated layer is typically less then 50 μm deep; this presents a problem when trying to obtain mechanical test data as a function of irradiation level. Two novel methodologies have been developed to record stress-strain curves for thin proton-irradiated surface layers of SA-508-4N ferritic steel. In the first case, in-situ loading experiments are carried out using a combination of X-ray diffraction and digital image correlation on the near surface region in order to measure stress and strain, thereby eliminating the influence of the non-irradiated volume. The second approach is to manufacture small-scale tensile specimens containing only the proton irradiated volume but approaching the smallest representative volume of the material. This is achieved by high-speed focused ion beam (FIB) milling though the application of a Xe+ Plasma-FIB (PFIB). It is demonstrated that both techniques are capable of recording the early stage of uniaxial flow behaviour of the irradiated material with sufficient accuracy providing a measure of irradiation-induced shift of yield strength, strain hardening and tensile strength.
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  • ar sensor that can detect trypanothione. The sensor includes a fluorescent protein, which changes its brightness based on its oxidation state, fused to the tryparedoxin protein. This probe could either be put in the cytosol or mitochondrion of Trypanosoma brucei cells. Treating the cells with hydrogen peroxide changed the fluorescence of the biosensor. Trypanosoma brucei cells without tryparedoxin protein in their cytosol still responded to an oxidative challenge in the mitochondrion. The experiments reveal that trypanosomes do have a mitochondrial trypanothione system. This new fluorescent biosensor will be used to study how other cellular compartments deal with oxidative conditions. The tests will reveal how different compartments communicate with each other to counteract the stress. The sensor could also be used to determine how anti-parasite drugs affect the cells’ trypanothione system. © 2020, Ebersoll et al.STUDY OBJECTIVES There are few studies evaluating 1. exercise capacity, as assessed by the six minutes walking distance test (6MWD) in large populations with obstructive sleep apnea (OSA); 2. correlations with patients' comorbidities. METHODS Cluster analysis on data of 1228 patients. Severity of exercise limitation was defined on the basis of 6MWD. RESULTS Sixty-one % showed exercise limitation (29.2 % and 31.9 % mild and severe exercise limitation, respectively). About 60 and 40 % of patients were included in cluster 1 (CL1) and 2 (CL2), respectively. CL1 included younger patients with high prevalence of apneas, desaturations, hypertension with better exercise tolerance. https://www.selleckchem.com/products/AZD5438.html CL2 included older patients, all COPD, high prevalence of chronic respiratory failure (CRF), less apneas but severe mean desaturation, daytime hypoxemia, more severe exercise limitation and exercise induced desaturations. Only chronic respiratory failure (CRF) and COPD, significantly (p less then 0.001) correlated with 6MWD less then 85% predicted. 6MWD correlated positively with apnea-hypopnea index, oxygen desaturation index, nocturnal SpO₂, resting arterial oxygen tension, mean SpO₂ on exercise, and negatively with age, body-mass index, time spent during night with SpO₂ less then 90%, mean nocturnal desaturation, arterial carbon dioxide tension and number of comorbidities. Patients without had higher exercise capacity than those with severe comorbidities, (p less then 0.001). Exercise limitation was significantly worse in OSA severity class I when compared to other classes (p less then 0.001). CONCLUSIONS High rate of OSA patients suffer from exercise limitation. Older age, comorbidities as COPD and CRF, OSA severity class I, severe mean nocturnal desaturation and daytime hypoxemia are associated with worse exercise tolerance. © 2020 American Academy of Sleep Medicine.OBJECTIVE Few studies have examined association between sleep duration trajectories and hypertension. This study aims to examine association of sleep duration trajectories with risk of hypertension and its related factors. METHODS This study used weight longitudinal data for 7,397 adults who provided valid responses in questionnaire with regard to information of sleep and hypertension from the China Health and Nutrition Survey (2004-2011). Subgroup analyses were included 5,532 participants who measured hypertension-related factors using blood samples. Latent class trajectory analysis was used to identify different sleep duration trajectories. Multivariate cox regression models and General linear regression models were used to assess association of trajectories with hypertension and its related factors. RESULTS Compared to stable sleep duration around 8 hours, the trajectory showing persist decrease as aging was significantly associated with increased risk of hypertension (HR1.12, 95%CI 1.01-1.24), while no significant association between trajectory showing increase to 9 hours as aging and risk of hypertension was observed (HR1.05, 95%CI 0.93-1.19). Further, uric acid levels, fasting glucose levels, TC levels and Apo-B levels were significantly higher in the trajectory showing persist decrease as aging than the other two trajectories (all P less then 0.05). CONCLUSIONS Decreasing sleep duration as aging is significantly associated with increased risk of hypertension and higher levels of its biomarkers throughout adulthood. © 2020 American Academy of Sleep Medicine.STUDY OBJECTIVES People show a facial recognition speed advantage, termed positive classification advantage (PCA), when judging whether a facial expression is happy compared to angry or sad. This study investigated emotional face recognition by patients with obstructive sleep apnea-hypopnea syndrome (OSAS) with impaired neurocognition. METHODS Thirty-four patients with OSAS and 26 healthy control patients who underwent 1 night of polysomnographic evaluation before recruitment were asked to complete an emotion recognition task. Accuracy rates and reaction times were recorded and analyzed using repeated-measures analysis of variance. RESULTS When participants were asked to classify positive (happy) versus negative (sad) emotional expressions, the phenomenon of PCA disappeared. Importantly, however, compared with the control patients who showed PCA, patients with OSAS identified sad faces faster but were similar in happy face processing. CONCLUSION In accordance with previous studies that showed depressive emotion in patients with OSAS, our results indicate that patients with OSAS show negative bias in facial expression recognition, which might lead to decline in ability of social communication. © 2020 American Academy of Sleep Medicine.STUDY OBJECTIVES To determine whether an intensive weight-loss program (IWLP) is effective for reducing weight, the severity of sleep apnea syndrome (OSA) and metabolic variables in patients with obesity and severe OSA undergoing continuous positive airway pressure treatment. METHODS 42 patients were randomized to the control (CG,n=20) or the intervention group (IG,n=22), who followed a 12-month IWLP. The primary outcome was a reduction in the apnea-hypopnea index (AHI) as measured at 3 and 12 months by full polysomnography. Metabolic variables, blood pressure, body fat composition by bioimpedance, carotid intima media thickness and visceral fat by computed tomography scan were also assessed. RESULTS Mean age was 49(6.7) years, body mass index 35(2.7) kg/m² and AHI 69(20) events/h. Weight reduction was higher for the IG than the CG at 3 and 12 months, -10.5 vs -2.3 kg (p less then 0.001), and -8.2 vs -0.1 kg (p less then 0.001), respectively, as was loss of visceral fat at 12 months. AHI decreased more in the IG at 3 months (-23.
    ar sensor that can detect trypanothione. The sensor includes a fluorescent protein, which changes its brightness based on its oxidation state, fused to the tryparedoxin protein. This probe could either be put in the cytosol or mitochondrion of Trypanosoma brucei cells. Treating the cells with hydrogen peroxide changed the fluorescence of the biosensor. Trypanosoma brucei cells without tryparedoxin protein in their cytosol still responded to an oxidative challenge in the mitochondrion. The experiments reveal that trypanosomes do have a mitochondrial trypanothione system. This new fluorescent biosensor will be used to study how other cellular compartments deal with oxidative conditions. The tests will reveal how different compartments communicate with each other to counteract the stress. The sensor could also be used to determine how anti-parasite drugs affect the cells’ trypanothione system. © 2020, Ebersoll et al.STUDY OBJECTIVES There are few studies evaluating 1. exercise capacity, as assessed by the six minutes walking distance test (6MWD) in large populations with obstructive sleep apnea (OSA); 2. correlations with patients' comorbidities. METHODS Cluster analysis on data of 1228 patients. Severity of exercise limitation was defined on the basis of 6MWD. RESULTS Sixty-one % showed exercise limitation (29.2 % and 31.9 % mild and severe exercise limitation, respectively). About 60 and 40 % of patients were included in cluster 1 (CL1) and 2 (CL2), respectively. CL1 included younger patients with high prevalence of apneas, desaturations, hypertension with better exercise tolerance. https://www.selleckchem.com/products/AZD5438.html CL2 included older patients, all COPD, high prevalence of chronic respiratory failure (CRF), less apneas but severe mean desaturation, daytime hypoxemia, more severe exercise limitation and exercise induced desaturations. Only chronic respiratory failure (CRF) and COPD, significantly (p less then 0.001) correlated with 6MWD less then 85% predicted. 6MWD correlated positively with apnea-hypopnea index, oxygen desaturation index, nocturnal SpO₂, resting arterial oxygen tension, mean SpO₂ on exercise, and negatively with age, body-mass index, time spent during night with SpO₂ less then 90%, mean nocturnal desaturation, arterial carbon dioxide tension and number of comorbidities. Patients without had higher exercise capacity than those with severe comorbidities, (p less then 0.001). Exercise limitation was significantly worse in OSA severity class I when compared to other classes (p less then 0.001). CONCLUSIONS High rate of OSA patients suffer from exercise limitation. Older age, comorbidities as COPD and CRF, OSA severity class I, severe mean nocturnal desaturation and daytime hypoxemia are associated with worse exercise tolerance. © 2020 American Academy of Sleep Medicine.OBJECTIVE Few studies have examined association between sleep duration trajectories and hypertension. This study aims to examine association of sleep duration trajectories with risk of hypertension and its related factors. METHODS This study used weight longitudinal data for 7,397 adults who provided valid responses in questionnaire with regard to information of sleep and hypertension from the China Health and Nutrition Survey (2004-2011). Subgroup analyses were included 5,532 participants who measured hypertension-related factors using blood samples. Latent class trajectory analysis was used to identify different sleep duration trajectories. Multivariate cox regression models and General linear regression models were used to assess association of trajectories with hypertension and its related factors. RESULTS Compared to stable sleep duration around 8 hours, the trajectory showing persist decrease as aging was significantly associated with increased risk of hypertension (HR1.12, 95%CI 1.01-1.24), while no significant association between trajectory showing increase to 9 hours as aging and risk of hypertension was observed (HR1.05, 95%CI 0.93-1.19). Further, uric acid levels, fasting glucose levels, TC levels and Apo-B levels were significantly higher in the trajectory showing persist decrease as aging than the other two trajectories (all P less then 0.05). CONCLUSIONS Decreasing sleep duration as aging is significantly associated with increased risk of hypertension and higher levels of its biomarkers throughout adulthood. © 2020 American Academy of Sleep Medicine.STUDY OBJECTIVES People show a facial recognition speed advantage, termed positive classification advantage (PCA), when judging whether a facial expression is happy compared to angry or sad. This study investigated emotional face recognition by patients with obstructive sleep apnea-hypopnea syndrome (OSAS) with impaired neurocognition. METHODS Thirty-four patients with OSAS and 26 healthy control patients who underwent 1 night of polysomnographic evaluation before recruitment were asked to complete an emotion recognition task. Accuracy rates and reaction times were recorded and analyzed using repeated-measures analysis of variance. RESULTS When participants were asked to classify positive (happy) versus negative (sad) emotional expressions, the phenomenon of PCA disappeared. Importantly, however, compared with the control patients who showed PCA, patients with OSAS identified sad faces faster but were similar in happy face processing. CONCLUSION In accordance with previous studies that showed depressive emotion in patients with OSAS, our results indicate that patients with OSAS show negative bias in facial expression recognition, which might lead to decline in ability of social communication. © 2020 American Academy of Sleep Medicine.STUDY OBJECTIVES To determine whether an intensive weight-loss program (IWLP) is effective for reducing weight, the severity of sleep apnea syndrome (OSA) and metabolic variables in patients with obesity and severe OSA undergoing continuous positive airway pressure treatment. METHODS 42 patients were randomized to the control (CG,n=20) or the intervention group (IG,n=22), who followed a 12-month IWLP. The primary outcome was a reduction in the apnea-hypopnea index (AHI) as measured at 3 and 12 months by full polysomnography. Metabolic variables, blood pressure, body fat composition by bioimpedance, carotid intima media thickness and visceral fat by computed tomography scan were also assessed. RESULTS Mean age was 49(6.7) years, body mass index 35(2.7) kg/m² and AHI 69(20) events/h. Weight reduction was higher for the IG than the CG at 3 and 12 months, -10.5 vs -2.3 kg (p less then 0.001), and -8.2 vs -0.1 kg (p less then 0.001), respectively, as was loss of visceral fat at 12 months. AHI decreased more in the IG at 3 months (-23.
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  • BACKGROUND Electronic medical record (EMR) systems capture large amounts of data per patient and present that data to physicians with little prioritization. Without prioritization, physicians must mentally identify and collate relevant data, an activity that can lead to cognitive overload. To mitigate cognitive overload, a Learning EMR (LEMR) system prioritizes the display of relevant medical record data. Relevant data are those that are pertinent to a context-defined as the combination of the user, clinical task, and patient case. To determine which data are relevant in a specific context, a LEMR system uses supervised machine learning models of physician information-seeking behavior. Since obtaining information-seeking behavior data via manual annotation is slow and expensive, automatic methods for capturing such data are needed. OBJECTIVE The goal of the research was to propose and evaluate eye tracking as a high-throughput method to automatically acquire physician information-seeking behavior useful for tiver operating characteristic curve (P=.40). CONCLUSIONS We used eye tracking to automatically capture physician information-seeking behavior and used it to train models for a LEMR system. The models that were trained using eye tracking performed like models that were trained using manual annotations. These results support further development of eye tracking as a high-throughput method for training clinical decision support systems that prioritize the display of relevant medical record data. ©Andrew J King, Gregory F Cooper, Gilles Clermont, Harry Hochheiser, Milos Hauskrecht, Dean F Sittig, Shyam Visweswaran. Originally published in the Journal of Medical Internet Research (http//www.jmir.org), 02.04.2020.BACKGROUND The worldwide expansion of preexposure prophylaxis (PrEP) with oral tenofovir-disoproxil-fumarate/emtricitabine will be critical to ending the HIV epidemic. However, maintaining daily adherence to PrEP can be difficult, and the accuracy of self-reported adherence is often limited by social desirability bias. Pharmacologic adherence monitoring (measuring drug levels in a biomatrix) has been critical to interpreting PrEP trials, but testing usually requires expensive equipment and skilled personnel. We have recently developed a point-of-care (POC) immunoassay to measure tenofovir in urine, allowing real-time adherence monitoring for the first time. OBJECTIVE The goal of this study is to examine a point-of-care adherence metric in PrEP to support and increase adherence via a randomized controlled trial. METHODS The paper describes the protocol for a pilot randomized controlled trial to test the acceptability, feasibility, and impact on long-term adherence of implementing a POC urine test to provide reir in hair. RESULTS This study has been funded by the National Institute of Health, approved by the Kenya Medical Research Institute Institutional Review Board, and will commence in June 2020. CONCLUSIONS A novel urine assay to measure and deliver information on adherence to PrEP in real-time will be tested for the first time in this trial planned among women on PrEP in Kenya. Study findings will inform a larger-scale trial assessing the impact of real-time adherence monitoring/feedback on HIV prevention. Improving adherence to PrEP will have long-term implications for efforts to end the HIV epidemic worldwide. TRIAL REGISTRATION ClinicalTrials.gov NCT03935464; https//clinicaltrials.gov/ct2/show/NCT03935464. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID) PRR1-10.2196/15029. ©Paul Drain, Kenneth Ngure, Nelly Mugo, Matthew Spinelli, Purba Chatterjee, Peter Bacchetti, David Glidden, Jared Baeten, Monica Gandhi. Originally published in JMIR Research Protocols (http//www.researchprotocols.org), 02.04.2020.BACKGROUND Acute respiratory infections (ARIs), primarily pneumonia, are the leading infectious cause of under-5 mortality worldwide. Manually counting respiratory rate (RR) for 60 seconds using an ARI timer is commonly practiced by community health workers to detect fast breathing, an important sign of pneumonia. https://www.selleckchem.com/products/gkt137831.html However, correctly counting breaths manually and classifying the RR is challenging, often leading to inappropriate treatment. A potential solution is to introduce RR counters, which count and classify RR automatically. OBJECTIVE This study aims to determine how the RR count of an Automated Respiratory Infection Diagnostic Aid (ARIDA) agrees with the count of an expert panel of pediatricians counting RR by reviewing a video of the child's chest for 60 seconds (reference standard), for children aged younger than 5 years with cough and/or difficult breathing. METHODS A cross-sectional study aiming to enroll 290 children aged 0 to 59 months presenting to pediatric in- and outpatient departments at a teacols (http//www.researchprotocols.org), 02.04.2020.BACKGROUND By enabling frequent, sensitive, and economic remote assessment, smartphones will facilitate the detection of early cognitive decline at scale. Previous studies have sustained participant engagement with remote cognitive assessment over a week; extending this to a period of 1 month clearly provides a greater opportunity for measurement. However, as study durations are increased, the need to understand how participant burden and scientific value might be optimally balanced also increases. OBJECTIVE This study explored the little but often approach to assessment employed by the Mezurio app when prompting participants to interact every day for over a month. Specifically, this study aimed to understand whether this extended duration of remote study is feasible, and which factors promote sustained participant engagement over such periods. METHODS A total of 35 adults (aged 40-59 years) with no diagnosis of cognitive impairment were prompted to interact with the Mezurio smartphone app platform for up to Chinner, Leona Wolters, Chris Hinds. Originally published in JMIR mHealth and uHealth (http//mhealth.jmir.org), 02.04.2020.BACKGROUND Smoking remains a leading cause of preventable death and illness. Internet interventions for smoking cessation have the potential to significantly impact public health, given their broad reach and proven effectiveness. Given the dose-response association between engagement and behavior change, identifying strategies to promote engagement is a priority across digital health interventions. Text messaging is a proven smoking cessation treatment modality and a powerful strategy to increase intervention engagement in other areas of health, but it has not been tested as an engagement strategy for a digital cessation intervention. OBJECTIVE This study examined the impact of 4 experimental text message design factors on adult smokers' engagement with an internet smoking cessation program. METHODS We conducted a 2×2×2×2 full factorial screening experiment wherein 864 participants were randomized to 1 of 16 experimental conditions after registering with a free internet smoking cessation program and enrolling in its automated text message program.
    BACKGROUND Electronic medical record (EMR) systems capture large amounts of data per patient and present that data to physicians with little prioritization. Without prioritization, physicians must mentally identify and collate relevant data, an activity that can lead to cognitive overload. To mitigate cognitive overload, a Learning EMR (LEMR) system prioritizes the display of relevant medical record data. Relevant data are those that are pertinent to a context-defined as the combination of the user, clinical task, and patient case. To determine which data are relevant in a specific context, a LEMR system uses supervised machine learning models of physician information-seeking behavior. Since obtaining information-seeking behavior data via manual annotation is slow and expensive, automatic methods for capturing such data are needed. OBJECTIVE The goal of the research was to propose and evaluate eye tracking as a high-throughput method to automatically acquire physician information-seeking behavior useful for tiver operating characteristic curve (P=.40). CONCLUSIONS We used eye tracking to automatically capture physician information-seeking behavior and used it to train models for a LEMR system. The models that were trained using eye tracking performed like models that were trained using manual annotations. These results support further development of eye tracking as a high-throughput method for training clinical decision support systems that prioritize the display of relevant medical record data. ©Andrew J King, Gregory F Cooper, Gilles Clermont, Harry Hochheiser, Milos Hauskrecht, Dean F Sittig, Shyam Visweswaran. Originally published in the Journal of Medical Internet Research (http//www.jmir.org), 02.04.2020.BACKGROUND The worldwide expansion of preexposure prophylaxis (PrEP) with oral tenofovir-disoproxil-fumarate/emtricitabine will be critical to ending the HIV epidemic. However, maintaining daily adherence to PrEP can be difficult, and the accuracy of self-reported adherence is often limited by social desirability bias. Pharmacologic adherence monitoring (measuring drug levels in a biomatrix) has been critical to interpreting PrEP trials, but testing usually requires expensive equipment and skilled personnel. We have recently developed a point-of-care (POC) immunoassay to measure tenofovir in urine, allowing real-time adherence monitoring for the first time. OBJECTIVE The goal of this study is to examine a point-of-care adherence metric in PrEP to support and increase adherence via a randomized controlled trial. METHODS The paper describes the protocol for a pilot randomized controlled trial to test the acceptability, feasibility, and impact on long-term adherence of implementing a POC urine test to provide reir in hair. RESULTS This study has been funded by the National Institute of Health, approved by the Kenya Medical Research Institute Institutional Review Board, and will commence in June 2020. CONCLUSIONS A novel urine assay to measure and deliver information on adherence to PrEP in real-time will be tested for the first time in this trial planned among women on PrEP in Kenya. Study findings will inform a larger-scale trial assessing the impact of real-time adherence monitoring/feedback on HIV prevention. Improving adherence to PrEP will have long-term implications for efforts to end the HIV epidemic worldwide. TRIAL REGISTRATION ClinicalTrials.gov NCT03935464; https//clinicaltrials.gov/ct2/show/NCT03935464. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID) PRR1-10.2196/15029. ©Paul Drain, Kenneth Ngure, Nelly Mugo, Matthew Spinelli, Purba Chatterjee, Peter Bacchetti, David Glidden, Jared Baeten, Monica Gandhi. Originally published in JMIR Research Protocols (http//www.researchprotocols.org), 02.04.2020.BACKGROUND Acute respiratory infections (ARIs), primarily pneumonia, are the leading infectious cause of under-5 mortality worldwide. Manually counting respiratory rate (RR) for 60 seconds using an ARI timer is commonly practiced by community health workers to detect fast breathing, an important sign of pneumonia. https://www.selleckchem.com/products/gkt137831.html However, correctly counting breaths manually and classifying the RR is challenging, often leading to inappropriate treatment. A potential solution is to introduce RR counters, which count and classify RR automatically. OBJECTIVE This study aims to determine how the RR count of an Automated Respiratory Infection Diagnostic Aid (ARIDA) agrees with the count of an expert panel of pediatricians counting RR by reviewing a video of the child's chest for 60 seconds (reference standard), for children aged younger than 5 years with cough and/or difficult breathing. METHODS A cross-sectional study aiming to enroll 290 children aged 0 to 59 months presenting to pediatric in- and outpatient departments at a teacols (http//www.researchprotocols.org), 02.04.2020.BACKGROUND By enabling frequent, sensitive, and economic remote assessment, smartphones will facilitate the detection of early cognitive decline at scale. Previous studies have sustained participant engagement with remote cognitive assessment over a week; extending this to a period of 1 month clearly provides a greater opportunity for measurement. However, as study durations are increased, the need to understand how participant burden and scientific value might be optimally balanced also increases. OBJECTIVE This study explored the little but often approach to assessment employed by the Mezurio app when prompting participants to interact every day for over a month. Specifically, this study aimed to understand whether this extended duration of remote study is feasible, and which factors promote sustained participant engagement over such periods. METHODS A total of 35 adults (aged 40-59 years) with no diagnosis of cognitive impairment were prompted to interact with the Mezurio smartphone app platform for up to Chinner, Leona Wolters, Chris Hinds. Originally published in JMIR mHealth and uHealth (http//mhealth.jmir.org), 02.04.2020.BACKGROUND Smoking remains a leading cause of preventable death and illness. Internet interventions for smoking cessation have the potential to significantly impact public health, given their broad reach and proven effectiveness. Given the dose-response association between engagement and behavior change, identifying strategies to promote engagement is a priority across digital health interventions. Text messaging is a proven smoking cessation treatment modality and a powerful strategy to increase intervention engagement in other areas of health, but it has not been tested as an engagement strategy for a digital cessation intervention. OBJECTIVE This study examined the impact of 4 experimental text message design factors on adult smokers' engagement with an internet smoking cessation program. METHODS We conducted a 2×2×2×2 full factorial screening experiment wherein 864 participants were randomized to 1 of 16 experimental conditions after registering with a free internet smoking cessation program and enrolling in its automated text message program.
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