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In the original publication [...].
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Particulate matter 2.5 (PM2.5) levels are associated with adverse pregnancy outcomes. In this retrospective cohort study, we examined whether the concentration of indoor PM2.5 affected pregnancy outcomes. Additionally, we evaluated biomarkers of pregnancy-related complications caused by fine dust. We collected clinical information and data based on residential addresses from the Air Korea database to assess PM2.5 exposure levels. As a multicenter prospective cohort study, we measured the indoor PM2.5 concentration and inflammatory and oxidative stress markers. The PM2.5 concentration of the low-birth-weight (LBW) delivery group was 27.21 µg/m3, which was significantly higher than that of the normal-birth-weight (NBW) group (26.23 µg/m3) (p = 0.02). When the newborns were divided by sex, the PM2.5 concentration of the LBW group was 27.89 µg/m3 in male infants, which was significantly higher than that of the NBW group (26.26 µg/m3) (p = 0.01). In the prospective study, 8-hydroxy-2-deoxyguanosine significantly increased in the high-concentration group (113.55 ng/mL, compared with 92.20 ng/mL in the low-concentration group); in the high-concentration group, the rates of preterm birth (PTB) and small size for gestational age significantly increased (p < 0.01, p = 0.01). This study showed an association between PM2.5, oxidative stress, and fetal growth, with the PTB group being more vulnerable.
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Multi-valued logic (MVL) technology that utilizes more than two logic states has recently been reconsidered because of the demand for greater power saving in current binary logic systems. Extensive efforts have been invested in developing MVL devices with multiple threshold voltages by adopting negative differential transconductance and resistance. In this study, a reconfigurable, multiple negative-differential-resistance (m-NDR) device with an electric-field-induced tunability of multiple threshold voltages is reported, which comprises a BP/ReS2 heterojunction and a ReS2 /h-BN/metal capacitor. Tunability for the m-NDR phenomenon is achieved via the resistance modulation of the ReS2 layer by electrical pulses applied to the capacitor region. Reconfigurability is verified in terms of the function of an MVL circuit composed of a reconfigurable m-NDR device and a load transistor, wherein staggered-type and broken-type double peak-NDR device operations are adopted for ternary inverter and latch circuits, respectively.
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Analyses of factor VIII procoagulant activity (FVIII:C) and the FVIII:C to VWF:Ag ratio (FVIII:C/VWF:Ag ratio) have been investigated as screening bioassays to detect haemophilia carriers. This study aimed to determine the validity of the FVIII:C/VWF:Ag ratio and FVIII:C analyses as screening tests. We reviewed the medical records of 137 genetically confirmed, proband haemophilia A patients and 179 of their familial females who had undergone carrier testing. The collected data included the severity and mutation type of F8 gene from probands and age, ABO blood type, FVIII:C, VWF:Ag, and the result of targeted gene analysis in females. We diagnosed 110 females as carriers, and their FVIII:C and FVIII:C/VWF:Ag ratio were lower than those in 69 non-carriers (FVIII:C: 59.3 IU/dL vs. 106.1 IU/dL, p = 0.000; FVIII:C/VWF:Ag ratio: 0.62 vs. 1.08, p = 0.000). In receiver operating characteristic analysis, the areas under the curve (AUC) of the FVIII:C/VWF:Ag ratio and FVIII:C were 0.936 and 0.876, respectively. The cut-off value of FVIII:C/VWF:Ag ratio (0.81) at the maximum Youden J index provided a sensitivity of 82.8% and specificity of 96.6%. The cut-off value of FVIII:C (83.8 IU/dL) showed a sensitivity of 81.8% and specificity of 79.7%. Considering the AUC, the FVIII:C/VWF:Ag ratio is a good screening test to detect haemophilia A carriers, as evidenced by its specificity of 96.6%; however, it may also induce false-negative results.
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Optogenetics refers to a technique that uses light to modulate neuronal activity with a high spatiotemporal resolution, which enables the manipulation of learning and memory functions in the human brain. This strategy of controlling neuronal activity using light can be applied for the development of intelligent systems, including neuromorphic and in-memory computing systems. Herein, a flexible van der Waals (vdW) optoelectronic synapse is reported, which is a core component of optogenetics-inspired intelligent systems. This synapse is fabricated on 2D vdW layered rhenium disulfide (ReS2 ) that features an inherent photosensitive memory nature derived from the persistent photoconductivity (PPC) effect, successfully mimicking the dynamics of biological synapses. Based on first-principles calculations, the PPC effect is identified to originate from sulfur vacancies in ReS2 that have an inherent tendency to form shallow defect states near the conduction band edges and under optical excitation lead to large lattice relaxation. Finally, the feasibility of applying the synapses in optogenetics-inspired intelligent systems is demonstrated via training and inference tasks for the CIFAR-10 dataset using a convolutional neural network composed of vdW optoelectronic synapse devices.
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Electrónica , Redes Neurales de la Computación , Optogenética , Biomimética/instrumentación , Biomimética/métodos , Conductividad Eléctrica , Luz , Renio/química , Sulfuros/química , Sinapsis/fisiologíaRESUMEN
The long-term plasticity of biological synapses was successfully emulated in an artificial synapse fabricated by combining low-surface defect van der Waals (vdW) and self-assembled (SA) materials. The synaptic operation could be achieved by facilitating hole trapping and releasing only via the amine (NH2) functional groups in 3-aminopropyltriethoxysilane, which consequently induced a gradual conductance change in the WSe2 channel. The vdW-SA synaptic device exhibited extremely stable long-term potentiation/depression (LTP/LTD) characteristics; its dynamic range and nonlinearity reproduced near 100 and 3.13/-6.53 (for LTP/LTD) with relative standard deviations (RSDs) below 2%. Furthermore, after conducting training and recognition tasks for the Modified National Institute of Standard and Technology (MNIST) digit patterns, we verified that the maximum recognition rate was 78.3%, and especially, its RSD was as low as 0.32% over several training/recognition cycles. This study provides a background for future research on advanced artificial synapses based on vdW and organic materials.
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Órganos Artificiales , Compuestos de Boro/química , Potenciación a Largo Plazo , Propilaminas/química , Silanos/química , Sinapsis/fisiología , Compuestos de Tungsteno/químicaRESUMEN
Multi-valued logic (MVL) technology is a promising approach for improving the data-handling capabilities and decreasing the power consumption of integrated circuits. This is especially attractive as conventional complementary metal-oxide-semiconductor technology is approaching its scaling and power density limits. Here, an ambipolar WSe2 field-effect transistor with two or more negative-differential-transconductance (NDT) regions in its transfer characteristic (NDTFET) is proposed for MVL applications of various radices. The operation and charge carrier transport mechanism of the NDTFET are studied first by Kelvin probe force microscopy, electrical, and capacitance-voltage measurements. Next, strategies for increasing the number of NDT regions and engineering the NDTFET transfer characteristic are discussed. Finally, the extensibility and tunability of our concept are demonstrated by adapting NDTFETs as core devices for ternary, quaternary, and quinary MVL inverters through simulations, where only WSe2 is employed as a channel material for all devices comprising the inverters. The MVL inverter operation principle and the mechanism of the multiple logic state formation are analyzed in detail. The proposed concept is practically verified by the fabrication of a ternary inverter.
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Inhibitor development is the most serious complication in patients with hemophilia. We investigated association of HLA genotypes with inhibitor development in Korean patients with severe hemophilia A (HA). HLA genotyping was done in 100 patients with severe HA including 27 patients with inhibitors. The allele frequencies between inhibitor-positive and inhibitor-negative patients were compared. HLA class I alleles were not associated with the inhibitor status. In HLA class II, DRB1*15 [n = 100, odds ratio (OR) 0.217, P = 0.028] and DPB1*05:01 [OR 0.461, P = 0.026] were negatively associated with inhibitor development. In a subgroup of patients with intron 22 inversion, C*07:02 was positively associated with inhibitor development [n = 30, OR 5.500, P = 0.043]. In the subgroup of patients without intron 22 inversion, the negative association between DPB1*05:01 and inhibitor development was reinforced [n = 70, OR 0.327, P = 0.010], and positive association of DRB1*13:02 and DPB1*04:01 with inhibitor development was identified [OR 3.059, P = 0.037 for both]. Previously reported risk alleles were not consistently associated with inhibitor risk in our series. This study demonstrated the profile of HLA alleles associated with inhibitor risk in Korean patients with severe HA was different from that in patients of other ethnicities, which needs to be considered in risk assessment and management.
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Inhibidores de Factor de Coagulación Sanguínea/sangre , Genotipo , Antígenos HLA-C/genética , Cadenas HLA-DRB1/genética , Hemofilia A/sangre , Hemofilia A/genética , Adolescente , Adulto , Anciano , Pueblo Asiatico , Inhibidores de Factor de Coagulación Sanguínea/genética , Niño , Preescolar , Femenino , Hemofilia A/epidemiología , Humanos , Lactante , Masculino , Persona de Mediana Edad , República de Corea/epidemiología , Factores de RiesgoRESUMEN
BACKGROUND: Korean National Health Insurance reimburses factor VIII (FVIII) and factor IX (FIX) clotting factor concentrate (CFC) infusions to discrepant activity levels, allowing elevation of FVIII activity to 60 IU/dL and FIX to 40 IU/dL. We aimed to assess hemostatic response to these target levels using global hemostatic assays. METHODS: We enrolled 34 normal healthy men, 34 patients with hemophilia A, and 36 with hemophilia B, with residual factor activity of 3 IU/dL or less and without inhibitors. Patients with hemophilia A and B received injected CFCs according to reimbursement guidelines. Fifteen minutes after injection, we assessed hemostatic response with global hemostatic assays: thrombin generation assay (TGA), thromboelastography (TEG), and clot waveform analysis (CWA). RESULTS: Normal healthy men and patients with hemophilia A and B were 36.7, 37.2, and 35.1 years old, respectively. FVIII and recombinant FIX concentrate doses were 28.8 IU/kg and 43.6 IU/kg. Post-infusion FVIII activity rose from 0.5 IU/dL to 69.4 IU/dL, while FIX activity rose from 1.4 IU/dL to 46.8 IU/dL. Post-infusion peak thrombin concentrations in hemophilia A and B were 116.6 nM/L and 76.4 nM/L (P<0.001). Post-infusion endogenous thrombin potential (ETP) in hemophilia A and B was 1349.8 nM/min and 915.6 nM (P<0.001). TEG index of hemophilia A and B was 0.11 and -0.51 (P=0.006). CONCLUSION: Current reimbursed doses for FIX concentrates are insufficient to achieve hemostatic responses comparable to those after reimbursed doses for FVIII concentrates in terms of peak thrombin concentration, ETP, and TEG index.
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BACKGROUND: A disease-causing mutation refers to a heritable genetic change that is associated with a specific phenotype (disease). The detection of a mutation from a patient's sample is critical for the diagnosis, treatment, and prognosis of the disease. There are numerous databases and applications with which to archive mutation data. However, none of them have been implemented with any automated bioinformatics tools for mutation detection and analysis starting from raw data materials from patients. We present a Locus Specific mutation DB (LSDB) construction system that supports both mutation detection and deposition in one package. RESULTS: COMUS (Clinician-Oriented locus specific MUtation detection and deposition System) is a mutation detection and deposition system for developing specific LSDBs. COMUS contains 1) a DNA sequence mutation analysis method for clinicians' mutation data identification and deposition and 2) a curation system for variation detection from clinicians' input data. To embody the COMUS system and to validate its clinical utility, we have chosen the disease hemophilia as a test database. A set of data files from bench experiments and clinical information from hemophilia patients were tested on the LSDB, KoHemGene http://www.kohemgene.org, which has proven to be a clinician-friendly interface for mutation detection and deposition. CONCLUSION: COMUS is a bioinformatics system for detecting and depositing new mutations from patient DNA with a clinician-friendly interface. LSDBs made using COMUS will promote the clinical utility of LSDBs. COMUS is available at http://www.comus.info.