Metabolic effects and cardiovascular disease risks of antiviral treatments in patients with chronic hepatitis B.

Different antiviral treatments for chronic hepatitis B (CHB) have been known to have different metabolic effects. This study aimed to reveal whether tenofovir alafenamide (TAF)-induced dyslipidemia and its associated outcomes are significant. This study utilized 15-year historical cohort including patients with CHB in Korea and consisted of two parts: the single-antiviral and switch-antiviral cohorts. In the single-antiviral cohort, patients were divided into four groups (entecavir [ETV]-only, tenofovir disoproxil fumarate [TDF]-only, TAF-only, and non-antiviral). Propensity score matching (PSM) and linear regression model were sequentially applied to compare metabolic profiles and estimated atherosclerotic cardiovascular disease (ASCVD) risks longitudinally. In the switch-antiviral cohort, pairwise analyses were conducted in patients who switched NAs to TAF or from TAF. In the single-antiviral cohort, body weight and statin use showed significant differences between groups before PSM, but well-balanced after PSM. Changes in total cholesterol were significantly different between groups (-2.57 mg/dL/year in the TDF-only group and +2.88 mg/dL/year in the TAF-only group; p = 0.002 and p = 0.02, respectively). In the TDF-only group, HDL cholesterol decreased as well (-0.55 mg/dL/year; p < 0.001). The TAF-only group had the greatest increase in ASCVD risk, followed by the TDF-only group and the non-antiviral group. In the switch-antiviral cohort, patients who switched from TDF to TAF had a higher total cholesterol after switching (+9.4 mg/dL/year) than before switching (-1.0 mg/dL/year; p = 0.047). Sensitivity analysis on data with an observation period set to a maximum of 3 years for NA treatment showed consistent results on total cholesterol (-2.96 mg/dL/year in the TDF-only group and +3.09 mg/dL/year in the TAF-only group; p = 0.001 and p = 0.005, respectively). Another sensitivity analysis conducted on statin-treated patients revealed no significant change in cholesterol and ASCVD risk. TAF was associated with increased total cholesterol, whereas TDF was associated with decreased total and HDL cholesterol. Both TAF and TDF were associated with increased ASCVD risks, and statin use might mitigate these risks.

Compact coherent perfect absorbers using topological guided-mode resonances.

We propose a topological coherent perfect absorber that enables almost ideal performance with remarkably compact device footprint and tight incident beams. The proposed structure is based on a topological junction of two guided-mode-resonance gratings. The structure provides robust systematic ways of remarkably tight lateral confinement of the absorbing resonance mode and near-perfect mode-match to arbitrary incident beams, which are unavailable with the conventional approaches. We demonstrate an exemplary amorphous Si thin-film structure that enables near-perfect absorptance modulation between 1.7 and 99% with device footprint width of 30-µm and 10-µm-wide incident Gaussian beams. Therefore, our proposed approach greatly improves practicality of guided-mode-resonance coherent perfect absorbers.

Topological beaming of light.

Nanophotonic light emitters are key components in numerous application areas because of their compactness and versatility. Here, we propose a topological beam emitter structure that takes advantage of submicrometer footprint size, small divergence angle, high efficiency, and adaptable beam shaping capability. The proposed structure consists of a topological junction of two guided-mode resonance gratings inducing a leaky Jackiw-Rebbi state resonance. The leaky Jackiw-Rebbi state leads to in-plane optical confinement with funnel-like energy flow and enhanced emission probability, resulting in highly efficient optical beam emission. In addition, the structure allows adaptable beam shaping for any desired positive definite profiles by means of Dirac mass distribution control, which can be directly encoded in lattice geometry parameters. Therefore, the proposed approach provides highly desirable properties for efficient micro-light emitters and detectors in various applications including display, solid-state light detection and ranging, laser machining, label-free sensors, optical interconnects, and telecommunications.

Geometric-phase intraocular lenses with multifocality.

We demonstrate a new type of multifocal and extended depth of focus (EDOF) intraocular lenses (IOLs) embedding µm-thin geometric phase (GP) lens layers. As an emerging approach for lens phase design, the GP modulated IOLs outperform conventional diffractive IOLs in multifocality while completely avoiding the clinically undesirable demand for additional surface patterns to standard monofocal IOL designs. The number of foci and light splitting ratio of the GP IOLs are adjusted by changing the number of stacked GP layers and the thickness of each layer. Bifocal and trifocal GP IOLs are fabricated by radial alignment of anisotropic orientation in UV-curable liquid crystal polymers. After characterizing the defocus image and modulation transfer function of the GP IOLs, it is expected that GP IOLs will alleviate the most common problems associated with multifocal and EDOF IOLs, blurred vision and photic phenomena caused by light scattering and posterior capsule opacification.

Inverse-cavity structure for low-threshold miniature lasers.

Creating micro and nano lasers, high threshold gain is an inherent problem that have critically restricted their great technological potentials. Here, we propose an inverse-cavity laser structure where its threshold gain in the shortest-cavity regime is order-of-magnitude lower than the conventional cavity configurations. In the proposed structure, a resonant feedback mechanism efficiently transfers external optical gain to the cavity mode at a higher rate for a shorter cavity, hence resulting in the threshold gain reducing with decreasing cavity length in stark contrast to the conventional cavity structures. We provide a fundamental theory and rigorous numerical analyses confirming the feasibility of the proposed structure. Remarkably, the threshold gain reduces down by a factor ~ 10-3 for a vertical-cavity surface-emitting laser structure and ~ 0.17 for a lattice-plasmonic nanocavity structure. Therefore, the proposed approach may produce extremely efficient miniature lasers desirable for variety of applications potentially beyond the present limitations.

Evaluation of Atopic Dermatitis and Cutaneous Infectious Disorders Using Sequential Pattern Mining: A Nationwide Population-Based Cohort Study.

According to previous studies, the increased risk of cutaneous infectious disorders in patients with atopic dermatitis (AD) is related to impaired epidermal function, abnormal systemic immune function, and lower antimicrobial peptides. In this study, we analyzed the association between AD and cutaneous infectious disorders in the real world using sequential pattern mining (SPM). We analyzed National Health Insurance data from 2010-2013 using SPM to identify comorbid cutaneous infectious diseases and the onset durations of comorbidities. Patients with AD were at greater risk for molluscum contagiosum (adjusted odds ratio (aOR), 5.273), impetigo (aOR, 2.852), chickenpox (aOR, 2.251), otitis media (aOR, 1.748), eczema herpeticum (aOR, 1.292), and viral warts (aOR, 1.105). In SPM analysis, comorbidity of 1.06% shown in molluscum contagiosum was the highest value, and the duration of 77.42 days documented for molluscum contagiosum was the shortest onset duration among all the association rules. This study suggests that AD is associated with an increased risk of cutaneous infectious disorders. In particular, care should be taken regarding its high relevance with impetigo, molluscum contagiosum, and otitis media, which may help in preventing AD from worsening through appropriately preventing and managing the condition.

Synthetic Topological Nodal Phase in Bilayer Resonant Gratings.

The notion of synthetic dimensions in artificial photonic systems has received considerable attention as it provides novel methods for exploring hypothetical topological phenomena as well as potential device applications. Here, we present nanophotonic manifestation of a two-dimensional topological nodal phase in bilayer resonant grating structures. Using the mathematical analogy between a topological semimetal and vertically asymmetric photonic lattices, we show that the interlayer shift simulates an extra momentum dimension for creating a two-dimensional topological nodal phase. We present a theoretical model and rigorous numerical analyses showing the two nodal points that produce a complex gapless band structure and localized edge states in the topologically nontrivial region. Therefore, our results provide a practical scheme for producing high-dimensional topological effects in simple low-dimensional photonic structures.

Optical Energy-Difference Conservation in a Synthetic Anti-PT-Symmetric System.

Anti-parity-time (APT) symmetry is associated with various effects beyond the fundamental limitations implied in the standard Hermitian-Hamiltonian dynamics. Here, we create an optical APT-symmetric system in a synthetic frequency domain using a conventional fiber without intrinsic gain or loss and experimentally reveal photonic APT-symmetric effects, including energy-difference conservation and synchronized power oscillation, which have not yet been confirmed experimentally in the optical domain. The optical fiber-based APT-symmetric system has a long interaction length because of its negligible loss, and the APT-symmetric Hamiltonian is precisely tunable with optical pumping density and phase mismatch. On this basis, we observe the phase transition at exceptional points, energy-difference conservation, and synchronized power oscillation. Our results provide a robust theoretical and experimental framework connecting the emerging non-Hermitian physics with technologically important nonlinear fiber-optic interactions.

Automated severity scoring of atopic dermatitis patients by a deep neural network.

Scoring atopic dermatitis (AD) severity with the Eczema Area and Severity Index (EASI) in an objective and reproducible manner is challenging. Automated measurement of erythema, papulation, excoriation, and lichenification severity using images has not yet been investigated. Our aim was to determine whether convolutional neural networks (CNNs) could assess erythema, papulation, excoriation, and lichenification severity at a level of competence comparable to dermatologists. We created a standard dataset of 8,000 clinical images showing AD. Each component of the EASI was scored from 0 to 3 by three dermatologists. We trained four CNNs (ResNet V1, ResNet V2, GoogLeNet, and VGG-Net) with the image dataset and determined which CNN was the most suitable for erythema, papulation, excoriation, and lichenification scoring. The brightness of the images in each dataset was adjusted to - 80% to + 80% of the original brightness (i.e., 9 levels by 20%) to investigate if the CNNs accurately measured scores if image brightness levels were changed. Compared to the dermatologists' scoring, accuracy rates of the CNNs were 99.17% for erythema, 93.17% for papulation, 96.00% for excoriation, and 97.17% for lichenification. CNNs trained with brightness-adjusted images achieved a high accuracy without the need to standardize camera settings. These results suggested that CNNs perform at level of competence comparable to dermatologists for scoring erythema, papulation, excoriation, and lichenification severity.

Monolithic focus-tunable lens technology enabled by disk-type dielectric-elastomer actuators.

We propose a monolithic focus-tunable lens structure based on the dielectric-elastomer actuator (DEA) technology. In our focus-tunable lens, a soft lens and radial in-plane actuator mimicking the ocular focal-tuning mechanism are constructed in a single body of an optimized dielectric-elastomer film. We provide device fabrication methods including elastomer synthesis, structure formation, and packaging process steps. Performance test measurements show 93% focal tunability and 7 ms response time under static and dynamic electrical driving conditions, respectively. These performance characteristics are substantially enhanced from the previous polylithic DEA tunable lens by a factor 1.4 for the focal tunability and a factor 9.4 for the dynamic tuning-speed limit. Therefore, we obtain greatly enhanced focal tuning control in a remarkably simple and compact device structure.

Facile Functionalization of Poly(Dimethylsiloxane) Elastomer by Varying Content of Hydridosilyl Groups in a Crosslinker.

Crosslinked poly(dimethylsiloxane) (PDMS) has been widely used as a dielectric elastomer for electrically driven actuators because it exhibits high elasticity, low initial modulus, and excellent moldability in spite of low dielectric constant. However, further improvement in the characteristics of the PDMS elastomer is not easy due to its chemical non-reactivity. Here, we report a simple method for functionalizing the elastomer by varying content of hydridosilyl groups in PDMS acted as a crosslinker. We synthesized poly(dimethylsiloxane-co-methylvinylsiloxane) (VPDMS) and poly(dimethylsiloxane-co-methylsiloxane) (HPDMS). Tri(ethylene glycol) divinyl ether (TEGDE) as a polar molecule was added to the mixture of VPDMS and HPDMS. TEGDE was reacted to the hydridosilyl group in HPDMS during crosslinking between VPDMS and HPDMS in the presence of platinum as a catalyst. Permittivity of the crosslinked film increased from ca. 25 to 36 pF/m at 10 kHz without a decline in other physical properties such as transparency and elasticity (T > 85%, E ~150 kPa, ɛ ~270%). It depends on the hydridosilyl group content of HPDMS. The chemical introduction of a new molecule into the hydridosilyl group in HPDMS during crosslinking would provide a facile, effective method of modifying the PDMS elastomers.

CMOS-compatible Si metasurface at visible wavelengths prepared by low-temperature green laser annealing.

A low-temperature laser crystallization is newly devised for producing polycrystalline silicon (poly-Si) thin films of low-loss, low surface roughness enough for nanoscale patterning, applicable to practical Si metasurface elements on complementary metal-oxide semiconductor (CMOS) electronic architectures in visible lights. The method is based on dielectric encapsulation of an amorphous Si film and subsequent laser-induced local crystallization. Such poly-Si thin film yields order-of-magnitude smaller surface roughness and grain size than those obtained with the conventional laser annealing processes. The mechanism of the formation of small and uniform crystalline grains during solidification is studied to ensure the smooth surfaces enough for nanoscale patterning. By obtaining root mean square of surface roughness <2.49 nm and extinction coefficient <4.8 × 10-2 at 550 nm, visible metasurface color-filter elements are experimentally demonstrated with the resonant transmission-peak efficiency approaching ∼85%. This low-loss poly-Si metasurface is favorably compatible with embedded CMOS electronic architectures in contrast to the conventional thermal annealing processes that often cause failure of electrical device functionalities due to delamination and material-property degradation problems. The proposed fabrication in this study provides a practical method for further development of various Si metasurfaces in the visible domain and their integration with CMOS electronic devices as well.

Evaluation of relationships between onychomycosis and vascular diseases using sequential pattern mining.

Onychomycosis (OM) is a common nail disease. Although controversial, vascular diseases are considered independent predictors of OM and vice versa. Sequential pattern mining (SPM) has not been previously used for statistical analysis in dermatology, but it is an efficient method for identifying frequent association rules in multiple sequential data sets. The aim of our study was to identify the relationship between OM and vascular diseases in the real world through a population-based study using SPM. We obtained population-based data recorded from 2002 to 2013 by the Health Insurance Research and Assessment Agency. Cases of vascular-related disease and OM were identified using the diagnostic codes of the International Classification of Diseases 10th Revision, version 2010. SPM measures were based on comorbidity and duration values. We estimated 3-year risk for progression from OM to vascular disease and vice versa using logistic regression. Patients with varicose veins and peripheral vascular disease had higher OM comorbidity (comorbidity: 1.26% and 0.69%, respectively) than did those with other vascular diseases. Patients diagnosed with varicose veins and peripheral vascular disease were diagnosed with OM after 25.50 and 55.10 days, respectively, which was a shorter duration than that observed for other diseases. Patients with OM were at higher risk for peripheral vascular disease (adjusted odds ratio (aOR) 1.199 [95% confidence interval (CI) 1.151-1.249]) and varicose veins (aOR 1.150 [95% CI 1.063-1.245]). Patients with peripheral vascular disease (aOR 1.128 [95% CI 1.081-1.177]) were at higher risk for OM, while patients with varicose veins had no significant risk for OM. Careful consideration of varicose veins or peripheral vascular disease is required for proper management of comorbidities in patients with OM.

Time-asymmetric loop around an exceptional point over the full optical communications band.

Topological operations around exceptional points1-8-time-varying system configurations associated with non-Hermitian singularities-have been proposed as a robust approach to achieving far-reaching open-system dynamics, as demonstrated in highly dissipative microwave transmission3 and cryogenic optomechanical oscillator4 experiments. In stark contrast to conventional systems based on closed-system Hermitian dynamics, environmental interferences at exceptional points are dynamically engaged with their internal coupling properties to create rotational stimuli in fictitious-parameter domains, resulting in chiral systems that exhibit various anomalous physical phenomena9-16. To achieve new wave properties and concomitant device architectures to control them, realizations of such systems in application-abundant technological areas, including communications and signal processing systems, are the next step. However, it is currently unclear whether non-Hermitian interaction schemes can be configured in robust technological platforms for further device engineering. Here we experimentally demonstrate a robust silicon photonic structure with photonic modes that transmit through time-asymmetric loops around an exceptional point in the optical domain. The proposed structure consists of two coupled silicon-channel waveguides and a slab-waveguide leakage-radiation sink that precisely control the required non-Hermitian Hamiltonian experienced by the photonic modes. The fabricated devices generate time-asymmetric light transmission over an extremely broad spectral band covering the entire optical telecommunications window (wavelengths between 1.26 and 1.675 micrometres). Thus, we take a step towards broadband on-chip optical devices based on non-Hermitian topological dynamics by using a semiconductor platform with controllable optoelectronic properties, and towards several potential practical applications, such as on-chip optical isolators and non-reciprocal mode converters. Our results further suggest the technological relevance of non-Hermitian wave dynamics in various other branches of physics, such as acoustics, condensed-matter physics and quantum mechanics.

Elastomer thin-film pressure sensor based on embedded photonic tunnel-junction arrays.

We propose an elastomer thin-film pressure sensor enabled by pressure-sensitive optical signals through vertical photonic tunnel-junction couplers. We provide the operation principle, design, fabrication, and test results from a 50 µm thick polydimethylsiloxane sheet accommodating embedded vertical photonic tunnel-junction couplers. The result with a 5 mm long device shows a differential optical power change that is ∼140% of the incident power under moderate external pressure of ∼40 kPa, thereby clearly demonstrating a robust pressure-sensing capability realized in a highly flexible, lightweight, transferrable, optically transparent, and bio-compatible thin-film material. Therefore, the proposed approach potentially enables versatile pressure and touch sensors for many applications in practice.

A Robust Soft Lens for Tunable Camera Application Using Dielectric Elastomer Actuators.

Developing tunable lenses, an expansion-based mechanism for dynamic focus adjustment can provide a larger focal length tuning range than a contraction-based mechanism. Here, we develop an expansion-tunable soft lens module using a disk-type dielectric elastomer actuator (DEA) that creates axially symmetric pulling forces on a soft lens. Adopted from a biological accommodation mechanism in human eyes, a soft lens at the annular center of a disk-type DEA pair is efficiently stretched to change the focal length in a highly reliable manner. A soft lens with a diameter of 3 mm shows a 65.7% change in the focal length (14.3-23.7 mm) under a dynamic driving voltage signal control. We confirm a quadratic relation between lens expansion and focal length that leads to large focal length tunability obtainable in the proposed approach. The fabricated tunable lens module can be used for soft, lightweight, and compact vision components in robots, drones, vehicles, and so on.

Observation of an anti-PT-symmetric exceptional point and energy-difference conserving dynamics in electrical circuit resonators.

Parity-time (PT) symmetry and associated non-Hermitian properties in open physical systems have been intensively studied in search of new interaction schemes and their applications. Here, we experimentally demonstrate an electrical circuit producing key non-Hermitian properties and unusual wave dynamics grounded on anti-PT (APT) symmetry. Using a resistively coupled amplifying-LRC-resonator circuit, we realize a generic APT-symmetric system that enables comprehensive spectral and time-domain analyses on essential consequences of the APT symmetry. We observe an APT-symmetric exceptional point (EP), inverse PT-symmetry breaking transition, and counterintuitive energy-difference conserving dynamics in stark contrast to the standard Hermitian dynamics keeping the system's total energy constant. Therefore, we experimentally confirm unique properties of APT-symmetric systems, and further development in other areas of physics may provide new wave-manipulation techniques and innovative device-operation principles.