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Open AccessArticle
The Arabidopsis Hypoxia Inducible AtR8 Long Non-Coding RNA also Contributes to Plant Defense and Root Elongation Coordinating with WRKY Genes under Low Levels of Salicylic Acid
Non-Coding RNA 2020, 6(1), 8; https://doi.org/10.3390/ncrna6010008 (registering DOI) - 26 Feb 2020
Abstract
AtR8 lncRNA was previously identified in the flowering plant Arabidopsis thaliana as an abundant Pol III-transcribed long non-coding RNA (lncRNA) of approximately 260 nt. AtR8 lncRNA accumulation is responsive to hypoxic stress and salicylic acid (SA) treatment in roots, but its function has [...] Read more.
AtR8 lncRNA was previously identified in the flowering plant Arabidopsis thaliana as an abundant Pol III-transcribed long non-coding RNA (lncRNA) of approximately 260 nt. AtR8 lncRNA accumulation is responsive to hypoxic stress and salicylic acid (SA) treatment in roots, but its function has not yet been identified. In this study, microarray analysis of an atr8 mutant and wild-type Arabidopsis indicated a strong association of AtR8 lncRNA with the defense response. AtR8 accumulation exhibited an inverse correlation with an accumulation of two WRKY genes (WRKY53/WRKY70) when plants were exposed to exogenous low SA concentrations (20 µM), infected with Pseudomonas syringae, or in the early stage of development. The highest AtR8 accumulation was observed 5 days after germination, at which time no WRKY53 or WRKY70 mRNA was detectable. The presence of low levels of SA resulted in a significant reduction of root length in atr8 seedlings, whereas wrky53 and wrky70 mutants exhibited the opposite phenotype. Taken together, AtR8 lncRNA participates in Pathogenesis-Related Proteins 1 (PR-1)-independent defense and root elongation, which are related to the SA response. The mutual regulation of AtR8 lncRNA and WRKY53/WRKY70 is mediated by Nonexpressor of Pathogenesis-Related Gene 1 (NPR1). Full article
Open AccessFeature PaperReview
The Potential Production of the Bioactive Compound Pinene Using Whey Permeate
Processes 2020, 8(3), 263; https://doi.org/10.3390/pr8030263 (registering DOI) - 26 Feb 2020
Abstract
Pinene is a secondary plant metabolite that has functional properties as a flavor additive as well as potential cognitive health benefits. Although pinene is present in low concentrations in several plants, it is possible to engineer microorganisms to produce pinene. However, feedstock cost [...] Read more.
Pinene is a secondary plant metabolite that has functional properties as a flavor additive as well as potential cognitive health benefits. Although pinene is present in low concentrations in several plants, it is possible to engineer microorganisms to produce pinene. However, feedstock cost is currently limiting the industrial scale-up of microbial pinene production. One potential solution is to leverage waste streams such as whey permeate as an alternative to expensive feedstocks. Whey permeate is a sterile-filtered dairy effluent that contains 4.5% weight/weight lactose, and it must be processed or disposed of due its high biochemical oxygen demand, often at significant cost to the producer. Approximately 180 million m3 of whey is produced annually in the U.S., and only half of this quantity receives additional processing for the recovery of lactose. Given that organisms such as recombinant Escherichia coli grow on untreated whey permeate, there is an opportunity for dairy producers to microbially produce pinene and reduce the biological oxygen demand of whey permeate via microbial lactose consumption. The process would convert a waste stream into a valuable coproduct. This review examines the current approaches for microbial pinene production, and the suitability of whey permeate as a medium for microbial pinene production. Full article
Open AccessFeature PaperArticle
Steel Wool for Water Treatment: Intrinsic Reactivity and Defluoridation Efficiency
Processes 2020, 8(3), 265; https://doi.org/10.3390/pr8030265 (registering DOI) - 26 Feb 2020
Abstract
Studies were undertaken to characterize the intrinsic reactivity of Fe0-bearing steel wool (Fe0 SW) materials using the ethylenediaminetetraacetate method (EDTA test). A 2 mM Na2-EDTA solution was used in batch and column leaching experiments. A total of 15 [...] Read more.
Studies were undertaken to characterize the intrinsic reactivity of Fe0-bearing steel wool (Fe0 SW) materials using the ethylenediaminetetraacetate method (EDTA test). A 2 mM Na2-EDTA solution was used in batch and column leaching experiments. A total of 15 Fe0 SW specimens and one granular iron (GI) were tested in batch experiments. Column experiments were performed with four Fe0 SW of the same grade but from various suppliers and the GI. The conventional EDTA test (0.100 g Fe0, 50 mL EDTA, 96 h) protocol was modified in two manners: (i) Decreasing the experimental duration (down to 24 h) and (ii) decreasing the Fe0 mass (down to 0.01 g). Column leaching studies involved glass columns filled to 1/4 with sand, on top of which 0.50 g of Fe0 was placed. Columns were daily gravity fed with EDTA and effluent analyzed for Fe concentration. Selected reactive Fe0 SW specimens were additionally investigated for discoloration efficiency of methylene blue (MB) in shaken batch experiments (75 rpm) for two and eight weeks. The last series of experiments tested six selected Fe0 SW for water defluoridation in Fe0/sand columns. Results showed that (i) the modifications of the conventional EDTA test enabled a better characterization of Fe0 SW; (ii) after 53 leaching events the Fe0 SW showing the best kEDTA value released the lowest amount of iron; (iii) all Fe0 specimens were efficient at discoloring cationic MB after eight weeks; (iv) limited water defluoridation by all six Fe0 SW was documented. Fluoride removal in the column systems appears to be a viable tool to characterize the Fe0 long-term corrosion kinetics. Further research should include correlation of the intrinsic reactivity of SW specimens with their efficiency at removing different contaminants in water. Full article
Open AccessArticle
Use of Alternative Wood for the Ageing of Brandy de Jerez
Foods 2020, 9(3), 250; https://doi.org/10.3390/foods9030250 (registering DOI) - 26 Feb 2020
Abstract
The use of alternative types of wood has arisen for the aging of the Brandy de Jerez, on a pilot plant level. In particular, besides the use of American oak, two more types of oak have been studied, French oak and Spanish oak, [...] Read more.
The use of alternative types of wood has arisen for the aging of the Brandy de Jerez, on a pilot plant level. In particular, besides the use of American oak, two more types of oak have been studied, French oak and Spanish oak, allowed by the Technical File for the ID Brandy de Jerez, and chestnut, which, though it is not officially allowed, is a type of wood which had been traditionally used in the area for the aging of wines and distillates. All of them have been studied with different toasting levels: Intense toasting and medium toasting. The study of the total phenolic composition (TPI), chromatic characteristics, organic acids, and sensory analysis have proven that chestnut leads to distillates with a higher amount of phenolic compounds and coloring intensity than oak. This behavior is the opposite as regards the toasting of the wood. Among the different types of oak, Spanish oak produces aged distillates with a higher phenolic composition and a higher color intensity. Regarding tasting, the best-assessed samples were those aged with chestnut, French oak, and American oak, and the assessors preferred those who had used a medium toasting level to those with an intense level. Full article
(This article belongs to the Special Issue New Insights into Spirit Beverages of Vitivinicultural Origin)
Open AccessArticle
New Radiation-Hardened Design of a CMOS Instrumentation Amplifier and its Tolerant Characteristic Analysis
Electronics 2020, 9(3), 388; https://doi.org/10.3390/electronics9030388 (registering DOI) - 26 Feb 2020
Abstract
A radiation-hardened instrumentation amplifier (IA) that allows precise measurement in radiation environments, including nuclear power plants, space environments, and radiation therapy rooms, was designed and manufactured, and its characteristics were verified. Most electronic systems are currently designed using silicon-based complementary metal-oxide semiconductor (CMOS) [...] Read more.
A radiation-hardened instrumentation amplifier (IA) that allows precise measurement in radiation environments, including nuclear power plants, space environments, and radiation therapy rooms, was designed and manufactured, and its characteristics were verified. Most electronic systems are currently designed using silicon-based complementary metal-oxide semiconductor (CMOS) integrated circuits (ICs) to achieve a highly integrated low-power design. However, fixed charges induced in silicon by ionization radiation cause various negative effects, resulting in, for example, the generation of leakage current in circuits, performance degradation, and malfunction. Given that such problems in radiation environments may directly lead to a loss of life or environmental contamination, it is critical to implement radiation-hardened CMOS IC technology. In this study, an IA used to amplify fine signals of the sensors was designed and fabricated in the 0.18 μm CMOS bulk process. The IA contained sub-circuits that ensured the stable voltage supply needed to implement system-on-chip (SoC) solutions. It was also equipped with special radiation-hardening technology by applying an I-gate n-MOSFET that blocks the radiation-induced leakage currents. Its ICs were verified to provide the intended performance following a total cumulative dose of up to 25 kGy(Si), ensuring its safety in radiation environments. Full article
(This article belongs to the Section Microelectronics and Optoelectronics)
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Open AccessFeature PaperArticle
Design of a Voltage to Time Converter with High Conversion Gain for Reliable and Secure Autonomous Vehicles
Electronics 2020, 9(3), 384; https://doi.org/10.3390/electronics9030384 (registering DOI) - 26 Feb 2020
Abstract
Automation of vehicles requires a secure, reliable, and real-time on-chip system. These systems also require very high-speed and compact on-chip analog to digital converters (ADC). The conventional ADC cannot fulfill this requirement. In this paper, we proposed a Darlington pair- and source biasing-based [...] Read more.
Automation of vehicles requires a secure, reliable, and real-time on-chip system. These systems also require very high-speed and compact on-chip analog to digital converters (ADC). The conventional ADC cannot fulfill this requirement. In this paper, we proposed a Darlington pair- and source biasing-based high speed, secure, and reliable voltage to time converter (VTC). It is a compact, high-speed design and gives high conversion gain. The source biasing also helps to increase the input voltage range. The conversion gain of the proposed circuit is 101.43ns/v, which is 52 times greater than the gain achieved by state-of-the-art design. It also shows less effect of process variation and bias temperature instability. Full article
Open AccessFeature PaperEditorial
Massive MIMO Systems: Present and Future
Electronics 2020, 9(3), 385; https://doi.org/10.3390/electronics9030385 (registering DOI) - 26 Feb 2020
(This article belongs to the Special Issue Massive MIMO Systems)
Open AccessArticle
Proteomic Analysis of Mucopolysaccharidosis IIIB Mouse Brain
Biomolecules 2020, 10(3), 355; https://doi.org/10.3390/biom10030355 (registering DOI) - 26 Feb 2020
Abstract
Mucopolysaccharidosis IIIB (MPS IIIB) is an inherited metabolic disease due to deficiency of α-N-Acetylglucosaminidase (NAGLU) enzyme with subsequent storage of undegraded heparan sulfate (HS). The main clinical manifestations of the disease are profound intellectual disability and neurodegeneration. A label-free quantitative proteomic approach was [...] Read more.
Mucopolysaccharidosis IIIB (MPS IIIB) is an inherited metabolic disease due to deficiency of α-N-Acetylglucosaminidase (NAGLU) enzyme with subsequent storage of undegraded heparan sulfate (HS). The main clinical manifestations of the disease are profound intellectual disability and neurodegeneration. A label-free quantitative proteomic approach was applied to compare the proteome profile of brains from MPS IIIB and control mice to identify altered neuropathological pathways of MPS IIIB. Proteins were identified through a bottom up analysis and 130 were significantly under-represented and 74 over-represented in MPS IIIB mouse brains compared to wild type (WT). Multiple bioinformatic analyses allowed to identify three major clusters of the differentially abundant proteins: proteins involved in cytoskeletal regulation, synaptic vesicle trafficking, and energy metabolism. The proteome profile of NAGLU−/− mouse brain could pave the way for further studies aimed at identifying novel therapeutic targets for the MPS IIIB. Data are available via ProteomeXchange with the identifier PXD017363. Full article
Open AccessFeature PaperArticle
Use of the Sol–Gel Method for the Preparation of Coatings of Titanium Substrates with Hydroxyapatite for Biomedical Application
Coatings 2020, 10(3), 203; https://doi.org/10.3390/coatings10030203 (registering DOI) - 26 Feb 2020
Abstract
Hydroxyapatite (HA) was coated onto the surface of commercially pure titanium grade 4 (a material generally used for implant application) by a dip coating method using HA sol. Hydroxyapatite sol was synthesized via sol–gel using Ca(NO3)2∙4H2O and [...] Read more.
Hydroxyapatite (HA) was coated onto the surface of commercially pure titanium grade 4 (a material generally used for implant application) by a dip coating method using HA sol. Hydroxyapatite sol was synthesized via sol–gel using Ca(NO3)2∙4H2O and P2O5 as precursors. The surface of the HA coating was homogeneous, as determined by scanning electron microscopy (SEM), attenuated total reflectance Fourier transform infrared (ATR-FTIR), and X-ray diffraction (XRD), which allowed the materials to be characterized. The bioactivity of the synthesized materials and their efficiency for use as future bone implants was confirmed by observing the formation of a layer of hydroxyapatite on the surface of the samples soaked in a fluid simulating the composition of human blood plasma. To verify the biocompatibility of the obtained biomaterial, fibroblasts were grown on a glass surface and were tested for viability after 24 h. The results of the WST-8 analysis suggest that the HA systems, prepared by the sol–gel method, are most suitable for modifying the surface of titanium implants and improving their biocompatibility. Full article
Open AccessArticle
Danegaptide Enhances Astrocyte Gap Junctional Coupling and Reduces Ischemic Reperfusion Brain Injury in Mice
Biomolecules 2020, 10(3), 353; https://doi.org/10.3390/biom10030353 - 26 Feb 2020
Abstract
Ischemic stroke is a complex and devastating event characterized by cell death resulting from a transient or permanent arterial occlusion. Astrocytic connexin43 (Cx43) gap junction (GJ) proteins have been reported to impact neuronal survival in ischemic conditions. Consequently, Cx43 could be a potential [...] Read more.
Ischemic stroke is a complex and devastating event characterized by cell death resulting from a transient or permanent arterial occlusion. Astrocytic connexin43 (Cx43) gap junction (GJ) proteins have been reported to impact neuronal survival in ischemic conditions. Consequently, Cx43 could be a potential target for therapeutic approaches to stroke. We examined the effect of danegaptide (ZP1609), an antiarrhythmic dipeptide that specifically enhances GJ conductance, in two different rodent stroke models. In this study, danegaptide increased astrocytic Cx43 coupling with no significant effects on Cx43 hemichannel activity, in vitro. Using matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI IMS) the presence of danegaptide within brain tissue sections were detected one hour after reperfusion indicating successful transport of the dipeptide across the blood brain barrier. Furthermore, administration of danegaptide in a novel mouse brain ischemia/reperfusion model showed significant decrease in infarct volume. Taken together, this study provides evidence for the therapeutic potential of danegaptide in ischemia/reperfusion stroke. Full article
Open AccessArticle
Hierarchical Nanoporous Sn/SnOx Systems Obtained by Anodic Oxidation of Electrochemically Deposited Sn Nanofoams
Nanomaterials 2020, 10(3), 410; https://doi.org/10.3390/nano10030410 (registering DOI) - 26 Feb 2020
Abstract
A simple two-step electrochemical method for the fabrication of a new type of hierarchical Sn/SnOx micro/nanostructures is proposed for the very first time. Firstly, porous metallic Sn foams are grown on Sn foil via hydrogen bubble-assisted electrodeposition from an acidulated tin chloride [...] Read more.
A simple two-step electrochemical method for the fabrication of a new type of hierarchical Sn/SnOx micro/nanostructures is proposed for the very first time. Firstly, porous metallic Sn foams are grown on Sn foil via hydrogen bubble-assisted electrodeposition from an acidulated tin chloride electrolyte. As-obtained metallic foams consist of randomly distributed dendrites grown uniformly on the entire metal surface. The estimated value of pore diameter near the surface is ~35 µm, while voids with a diameter of ~15 µm appear in a deeper part of the deposit. Secondly, a layer of amorphous nanoporous tin oxide (with a pore diameter of ~60 nm) is generated on the metal surface by its anodic oxidation in an alkaline electrolyte (1 M NaOH) at the potential of 4 V for various durations. It is confirmed that if only optimal conditions are applied, the dendritic morphology of the metal foam does not change significantly, and an open-porous structure is still preserved after anodization. Such kinds of hierarchical nanoporous Sn/SnOx systems are superhydrophilic, contrary to those obtained by thermal oxidation of metal foams which are hydrophobic. Finally, the photoelectrochemical activity of the nanostructured metal/metal oxide electrodes is also presented. Full article
(This article belongs to the Special Issue Advances in Electrochemical Fabrication of Nanoporous Materials)
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Open AccessArticle
Investigating Thermal Performance of Residential Buildings in Marmari Region, South Evia, Greece
Challenges 2020, 11(1), 5; https://doi.org/10.3390/challe11010005 (registering DOI) - 26 Feb 2020
Abstract
In recent decades, the steady increase of energy consumption from building construction and operations cause atmospheric pollution and significant financial burden, mainly due to the high costs imposed from energy production. This study examines ways under which modern designs of a building can [...] Read more.
In recent decades, the steady increase of energy consumption from building construction and operations cause atmospheric pollution and significant financial burden, mainly due to the high costs imposed from energy production. This study examines ways under which modern designs of a building can be applied on construction and domestication while following conventional methods of construction, compared to a building that has been constructed and domesticated under bioclimatic architecture. Particularly, two buildings were investigated in terms of the energy consumption incurred, being built on the same seaside area and period of construction and at adjacent plots of the same distance from sea for ease of comparison. The first building (A1) was constructed under the principles of bioclimatic architecture, being also facilitated with green and smart technologies. The second building (A2) was constructed under conventional construction techniques. The energy efficiency of both buildings was calculated by the “TEE KENAK” software, while specific parameters were recorded. Energy classifications of both buildings were valued and a proposed scenario and interventions unveiled the energy classification upgrading from A2 to A1. Our analysis revealed, as also found in the literature, that during thermal energy oscillating conditions, corresponding relative humidity stresses were observed, indicating that the vapor pressure handling should be taken into account towards comfort. The preliminary incremental cost evaluation and comparison of A1 and A2 energy upgrading under the criterion of simple payback period were critically discussed. Full article
Open AccessArticle
Improving Coastal Ocean Wave Height Forecasting during Typhoons by using Local Meteorological and Neighboring Wave Data in Support Vector Regression Models
J. Mar. Sci. Eng. 2020, 8(3), 149; https://doi.org/10.3390/jmse8030149 (registering DOI) - 26 Feb 2020
Abstract
This study is aimed at applying support vector regression to perform realtime typhoon wave height forecasting with lead times of 1 to 3 h. Two wave rider buoys in the coastal ocean northeast of Taiwan provided realtime observation wave and meteorological data for [...] Read more.
This study is aimed at applying support vector regression to perform realtime typhoon wave height forecasting with lead times of 1 to 3 h. Two wave rider buoys in the coastal ocean northeast of Taiwan provided realtime observation wave and meteorological data for the study. Information from actual typhoon events was collected and used for model calibration and validation. Three model structures were developed with different combinations of input variables, including wave, typhoon, and meteorological data. Analysis of forecasting results indicated that the proposed models have good generalization ability, but forecasts with longer lead times underestimate extreme wave heights. Comparisons of models with different inputs indicated that adding local meteorological data enhanced forecasting accuracy. Backup models were also developed in case local wave and meteorological data were unavailable. Analysis of these models revealed that when local wave heights are unknown, using neighboring wave heights can improve forecasting performance. Full article
(This article belongs to the Special Issue Coastal Flooding and Protection)
Open AccessArticle
Innovative Poly (Vinylidene Fluoride) (PVDF) Electrospun Nanofiber Membrane Preparation Using DMSO as a Low Toxicity Solvent
Membranes 2020, 10(3), 36; https://doi.org/10.3390/membranes10030036 (registering DOI) - 26 Feb 2020
Abstract
Electrospinning is an emerging technique for the preparation of electrospun fiber membranes (ENMs), and a very promising one on the basis of the high-yield and the scalability of the process according to a process intensification strategy. Most of the research reported in the [...] Read more.
Electrospinning is an emerging technique for the preparation of electrospun fiber membranes (ENMs), and a very promising one on the basis of the high-yield and the scalability of the process according to a process intensification strategy. Most of the research reported in the literature has been focused on the preparation of poly (vinylidene fluoride) (PVDF) ENMs by using N,N- dimethylformamide (DMF) as a solvent, which is considered a mutagenic and cancerogenic substance. Hence, the possibility of using alternative solvents represents an interesting approach to investigate. In this work, we explored the use of dimethyl sulfoxide (DMSO) as a low toxicity solvent in a mixture with acetone for the preparation of PVDF-ENMs. As a first step, a solubility study of the polymer, PVDF 6012 Solef®, in several DMSO/acetone mixtures was carried out, and then, different operating conditions (e.g., applied voltage and needle to collector plate distance) for the successful electrospinning of the ENMs were evaluated. The study provided evidence of the crucial role of solution conductivity in the electrospinning phase and the thermal post-treatment. The prepared ENMs were characterized by evaluating the morphology (by SEM), pore-size, porosity, surface properties, and performance in terms of water permeability. The obtained results showed the possibility of producing ENMs in a more sustainable way, with a pore size in the range of 0.2-0.8 µm, high porosity (above 80%), and water flux in the range of 11.000–38.000 L/m2·h·bar. Full article
(This article belongs to the Special Issue Membrane Processes and Materials for a Sustainable Bioeconomy)
Open AccessArticle
Mainstreaming Climate-Smart Agriculture in Small-Scale Farming Systems: A Holistic Nonparametric Applicability Assessment in South Africa
Agriculture 2020, 10(3), 52; https://doi.org/10.3390/agriculture10030052 (registering DOI) - 26 Feb 2020
Abstract
Current research focuses disproportionately on the characteristics of farmers to understand the factors that influence the introduction of climate-smart agriculture (CSA). As a result, there has been a failure to take a holistic view of the range of drivers and barriers to CSA [...] Read more.
Current research focuses disproportionately on the characteristics of farmers to understand the factors that influence the introduction of climate-smart agriculture (CSA). As a result, there has been a failure to take a holistic view of the range of drivers and barriers to CSA implementation. Many aspects of technologies or practices that may encourage or inhibit the implementation of CSA and define its applicability are, therefore, not systematically considered in the design of interventions. The uptake of any practice should depend on both farmers’ characteristics and factors inherent in the practice itself. This paper, therefore, examines procedures for incorporating the applicability of CSA practices in a farm-level analysis based on the investigations conducted in King Cetshwayo District Municipality (KCDM) of the KwaZulu-Natal (KZN) Province of South Africa. How the farmers perceived the social, technical, economic, and environmental compatibility of the practices constituted the key goal of the inquiry. Data were collected through structured interviews using close-ended questionnaires, from a sample of 327 small-scale farmers (farmers with farm sizes of less than or equal to 5 hectares). The analysis made use of the Acceptance Level Index (ALI) and Composite Score Index (CSI). This paper establishes that, based on social compatibility, the farmers showed high acceptance for cultivation of cover crops (ALI = 574), agroforestry (ALI = 559), and diet improvement for animals (ALI = 554), based on technical compatibility, the use of organic manure (ALI = 545), rotational cropping (ALI = 529), mulching (ALI = 525) and cultivation of cover crops (ALI = 533) were highly accepted. With economic compatibility in perspective, the farmers showed high preference for mulching (ALI = 541), organic manure (ALI = 542) and rotational cropping (ALI = 515), while the use of organic manure (ALI = 524) was highly embraced based on environmental compatibility. Consequently, it is recommended that policies aimed at mainstreaming CSA technologies should pay adequate attention to their applicability in locations under consideration and emphasize the critical role of the provision of information on CSA technologies or practices. Full article
Open AccessCommentary
Going Beyond Conventional Mammographic Density to Discover Novel Mammogram-Based Predictors of Breast Cancer Risk
J. Clin. Med. 2020, 9(3), 627; https://doi.org/10.3390/jcm9030627 (registering DOI) - 26 Feb 2020
Abstract
This commentary is about predicting a woman’s breast cancer risk from her mammogram, building on the work of Wolfe, Boyd and Yaffe on mammographic density. We summarise our efforts at finding new mammogram-based risk predictors, and how they combine with the conventional mammographic [...] Read more.
This commentary is about predicting a woman’s breast cancer risk from her mammogram, building on the work of Wolfe, Boyd and Yaffe on mammographic density. We summarise our efforts at finding new mammogram-based risk predictors, and how they combine with the conventional mammographic density, in predicting risk for interval cancers and screen-detected breast cancers across different ages at diagnosis and for both Caucasian and Asian women. Using the OPERA (odds ratio per adjusted standard deviation) concept, in which the risk gradient is measured on an appropriate scale that takes into account other factors adjusted for by design or analysis, we show that our new mammogram-based measures are the strongest of all currently known breast cancer risk factors in terms of risk discrimination on a population-basis. We summarise our findings graphically using a path diagram in which conventional mammographic density predicts interval cancer due to its role in masking, while the new mammogram-based risk measures could have a causal effect on both interval and screen-detected breast cancer. We discuss attempts by others to pursue this line of investigation, the measurement challenge that allows different measures to be compared in an open and transparent manner on the same datasets, as well as the biological and public health consequences. Full article
(This article belongs to the Special Issue Mammographic Density: Biology and Clinical Applications)
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