Influenza vaccine effectiveness against hospitalized SARS-CoV-2 infection.

Background: Some studies conducted before the Delta and Omicron variant-dominant periods have indicated that influenza vaccination provided protection against COVID-19 infection or hospitalization, but these results were limited by small study cohorts and a lack of comprehensive data on patient characteristics. No studies have examined this question during the Delta and Omicron periods (08/01/2021 to 2/22/2022). Methods: We conducted a retrospective cohort study of influenza-vaccinated and unvaccinated patients in the Corewell Health East(CHE, formerly known as Beaumont Health), Corewell Health West(CHW, formerly known as Spectrum Health) and Michigan Medicine (MM) healthcare system during the Delta-dominant and Omicron-dominant periods. We used a test-negative, case-control analysis to assess the effectiveness of the influenza vaccine against hospitalized SARS-CoV-2 outcome in adults, while controlling for individual characteristics as well as pandameic severity and waning immunity of COVID-19 vaccine. Results: The influenza vaccination has shown to provided some protection against SARS-CoV-2 hospitalized outcome across three main healthcare systems. CHE site (odds ratio [OR]=0.73, vaccine effectiveness [VE]=27%, 95% confidence interval [CI]: [18-35], p<0.001), CHW site (OR=0.85, VE=15%, 95% CI: [6-24], p<0.001), MM (OR=0.50, VE=50%, 95% CI: [40-58], p <0.001) and overall (OR=0.75, VE=25%, 95% CI: [20-30], p <0.001). Conclusion: The influenza vaccine provides a small degree of protection against SARS-CoV-2 infection across our study sites.

Bi-Layer nanoimprinting lithography for metal-assisted chemical etching with application on silicon mold replication.

This paper reports a new type of nanoimprinting method called Bi-layer nanoimprinting lithography (BL-NIL), which can work along with metal-assisted chemical etching (MaCE) for fabricating nanostructures on silicon. In contrast to conventional nanoimprinting techniques, BL-NIL adds an interposing layer between the imprinting resist layer and silicon substrate. After the standard imprinting process, dry etching was used to etch away the residual imprinting layer and part of the interposing layer. Finally, the remaining interposing layer was wet-etched using its remover. This innovative approach can ensure cleanliness at the metal/silicon interface after metal lift-off processes, and therefore guarantees the success of MaCE. By combining BL-NIL and MaCE, expensive silicon molds with sub-micrometer/nanometer-scale feature sizes can be easily replicated and preserved. This is important for the application of nanoimprinting technologies in industrial manufacturing.

Maskless lithography for large area patterning of three-dimensional microstructures with application on a light guiding plate.

This paper presents a maskless lithography system that can perform three-dimensional (3D) ultraviolet (UV) patterning on a photoresist (PR) layer. After PR developing processes, patterned 3D PR microstructures over a large area are obtained. This maskless lithography system utilizes an UV light source, a digital micromirror device (DMD), and an image projection lens to project a digital UV image on the PR layer. The projected UV image is then mechanically scanned over the PR layer. An UV patterning scheme based on the idea of obliquely scanning and step strobe lighting (OS3L) is developed to precisely control the spatial distribution of projected UV dose, such that desired 3D PR microstructures can be obtained after PR development. Two types of concave microstructures with truncated conical and nuzzle-shaped cross-sectional profiles are experimentally obtained over a patterning area of 160 ×115 mm2. These patterned microstructures are then used for replicating nickel molds and for mass-production of light-guiding plates used in back-lighting and display industry. Potential improvements and advancements of the proposed 3D maskless lithography technique for future applications will be addressed.

Immune Checkpoint Inhibitors and Risk of Type 1 Diabetes.

OBJECTIVE: Type 1 diabetes mellitus (T1DM) is a rare, irreversible immune-related adverse event reported in patients receiving treatment with immune checkpoint inhibitors (ICI). However, clinical risk factors for ICI-induced T1DM (ICI-T1DM) and its impact on survival in patients remain unknown. RESEARCH DESIGN AND METHODS: We used Optum's Clinformatics Data Mart database for assessment of the incidence and characteristics of T1DM in a large de-identified cohort of patients treated with ICI between 2017 and 2020. We applied Fine-Gray and cause-specific hazard models to study associations between patient/treatment characteristics and ICI-T1DM and applied the Cox model with ICI-T1DM as a time-varying covariate to assess the impact of ICI-T1DM on survival. RESULTS: ICI-T1DM was observed in 261 of 30,337 (0.86%) patients. Dual use of antibodies to cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed cell death 1 (PD-1) or programmed cell death ligand 1 (PD-L1) was associated with increasing risk of ICI-T1DM (hazard ratio [HR] 1.62; 95% CI 1.15-2.26) vs. anti-PD-L1 or anti-PD-1 alone. Younger age (HR 1.19 for every 5-year decrease; 95% CI 1.13-1.25) and preexisting non-T1DM diabetes (HR 4.48; 95% CI 3.45-5.83) were also associated with higher risk of ICI-T1DM. Conversely, prior use of immunosuppressive medications (HR 0.57; 95% CI 0.34-0.95) was associated with lower incidence of ICI-T1DM, but part of its protective effect may be due to the increased mortality rate. Development of ICI-T1DM does not seem to significantly impact patient survival. CONCLUSIONS: The risk of ICI-T1DM is associated with the type of ICI therapy, patient age, and preexisting non-T1DM diabetes. These data may help guide risk assessment and screening practices for patients during ICI therapy.

Ultrasonic Touch Sensing System Based on Lamb Waves and Convolutional Neural Network.

A tactile position sensing system based on the sensing of acoustic waves and analyzing with artificial intelligence is proposed. The system comprises a thin steel plate with multiple piezoelectric transducers attached to the underside, to excite and detect Lamb waves (or plate waves). A data acquisition and control system synchronizes the wave excitation and detection and records the transducer signals. When the steel plate is touched by a finger, the waveform signals are perturbed by wave absorption and diffraction effects, and the corresponding changes in the output signal waveforms are sent to a convolutional neural network (CNN) model to predict the x- and y-coordinates of the finger contact position on the sensing surface. The CNN model is trained by using the experimental waveform data collected using an artificial finger carried by a three-axis motorized stage. The trained model is then used in a series of tactile sensing experiments performed using a human finger. The experimental results show that the proposed touch sensing system has an accuracy of more than 95%, a spatial resolution of 1 × 1 cm2, and a response time of 60 ms.

Simple In-House Fabrication of Microwells for Generating Uniform Hepatic Multicellular Cancer Aggregates and Discovering Novel Therapeutics.

Three-dimensional (3D) cell culture models have become powerful tools because they better simulate the in vivo pathophysiological microenvironment than traditional two-dimensional (2D) monolayer cultures. Tumor cells cultured in a 3D system as multicellular cancer aggregates (MCAs) recapitulate several critical in vivo characteristics that enable the study of biological functions and drug discovery. The microwell, in particular, has emerged as a revolutionary technology in the generation of MCAs as it provides geometrically defined microstructures for culturing size-controlled MCAs amenable for various downstream functional assays. This paper presents a simple and economical microwell fabrication methodology that can be conveniently incorporated into a conventional laboratory setting and used for the discovery of therapeutic interventions for liver cancer. The microwells were 400-700 µm in diameter, and hepatic MCAs (Huh-7 cells) were cultured in them for up to 5 days, over which time they grew to 250-520 µm with good viability and shape. The integrability of the microwell fabrication with a high-throughput workflow was demonstrated using a standard 96-well plate for proof-of-concept drug screening. The IC50 of doxorubicin was determined to be 9.3 µM under 2D conditions and 42.8 µM under 3D conditions. The application of photothermal treatment was demonstrated by optimizing concanavalin A-FITC conjugated silica-carbon hollow spheres (SCHSs) at a concentration of 500:200 µg/mL after a 2 h incubation to best bind with MCAs. Based on this concentration, which was appropriate for further photothermal treatment, the relative cell viability was assessed through exposure to a 3 W/cm2 near-infrared laser for 20 min. The relative fluorescence intensity showed an eight-fold reduction in cell viability, confirming the feasibility of using photothermal treatment as a potential therapeutic intervention. The proposed microwell integration is envisioned to serve as a simple in-house technique for the generation of MCAs useful for discovering therapeutic modalities for liver cancer treatment.

Contact Photolithography at Sub-Micrometer Scale Using a Soft Photomask.

This paper proposes a method for improving the patterning resolution of conventional contact photolithography from the micrometer, down to the sub-micrometer scale. The key element is a soft polydimethylsiloxane (PDMS) photomask, which is first replicated from a silicon mold and then patterned with a black photoresist (PR) layer to selectively block ultraviolet (UV) light. This soft PDMS photomask can easily form an intimate and conformable contact with a PR-coated substrate and hence can perform contact photolithography with high pattern resolution. The fabrication processes of this black-PR/PDMS soft photomask are experimentally carried out. Using the fabricated soft photomask, UV patterning by contact photolithography with the smallest line-width of 170 nm over a 4" wafer area was successfully achieved. The advantages and potentials of this new type of contact photolithography will be addressed.

Waveguide Plasmon Resonance of Arrayed Metallic Nanostructures Patterned on a Soft Substrate by Direct Contact Printing Lithography.

This paper presents a direct contact printing method to obtain arrayed metallic nanostructures on a soft polymer substrate. It utilizes a polydimethylsiloxane (PDMS) mold replicated from silicon molds to transfer metallic nanopatterns onto a polymer substrate based on differences in interfacial bonding energy. Arrayed metallic nanodisks with a disk diameter down to 180 nm and a center-to-center pitch around 400 nm are experimentally patterned on a PET substrate. The patterned metallic nanostructures are then spin-coated with a polymer layer; which mechanically secures the patterned nanostructures and optically allows waveguide plasmon resonance being excited by incident EM waves. Both experimental works and theoretical modeling are given to illustrate the behaviors of different types of plasmon resonance. These arrayed metallic nanostructures patterned on a soft polymer substrate and their tunable optical characteristics open up many possibilities in future engineering applications.

Contact photolithography using a carbon-black embedded soft photomask and ultraviolet light emitting diodes with application on patterned sapphire substrates.

This paper presents a contact photolithography method for large-area ultraviolet (UV) patterning using a soft polydimethylsiloxane (PDMS) photomask and a planar light source consisting of arrayed light-emitting diodes (LEDs). With simple design and construction, the UV light source can achieve uniformly distributed UV light intensity over an area of 4" in diameter but its divergent angle is 15°. To overcome this large divergent angle, a PDMS soft mold embedded with carbon-black inserts as the UV light blocking materials is applied. It is demonstrated that, when increasing the aspect ratio of the carbon-black inserts, one can achieve excellent UV patterning results. Both experimental data and simulation results are presented. This contact photolithography system has been successfully used for manufacturing patterned sapphire substrates (PSSs) in LED industry. The advantages and potential applications of the proposed method will be addresses.

Measurement of circumferential Lamb waves using a line-focus poly(vinylidene fluoride) transducer and cross correlation waveform analysis.

This paper presents a method for measuring circumferential Lamb waves propagating on a cylindrically curved thin plate. The measurement is carried out using a wideband and line-focused poly(vinylidene fluoride) transducer along with a defocusing waveform measurement method. After synthesizing the acquired waveforms, interference patterns can be obtained and a cross correlation method is developed to accurately extract the wave velocity as a function of wave frequency. Using three stainless steel thin plates of different thicknesses (100, 150, and 300 µm) and a radius of curvature of 10 mm, dispersion curves for several fundamental and higher order modes of circumferential Lamb waves are simultaneously determined. Theoretical dispersion curves are also calculated and compared with their experimental counterparts. Very good agreements are observed, which concludes the measurement accuracy of this measurement method.

Beam pen lithography based on focused laser diode beam with single microlens fabricated by excimer laser.

A method is proposed to minimize the focused spot size of an elliptically-diverging laser diode beam by means of a circular aperture and a single plano-convex aspherical microlens. The proposed microlens is fabricated using an excimer laser dragging method and has two different profiles in the x- and y-axis directions. The focused spot size of the beam is examined both numerically and experimentally. The feasibility of the proposed approach for beam pen lithography applications is demonstrated by patterning dotted, straight-line and spiral features on a photo resist layer followed by thin gold layer deposition and metal lift-off. The minimum feature size for dotted pattern is around 2.57 µm, while the minimum line-widths for straight-line and spiral pattern are 3.05 µm and 4.35 µm, respectively. Thus, the technique can be applied to write any arbitrary pattern for high-resolution lithography.

Apertureless beam pen lithography based on fully metal-coated polyurethane-acrylate (PUA) pyramidal microstructure array.

This work demonstrates a form of arrayed transmitting apertureless near-field photolithography, called apertureless beam pen lithography. An array of fully chromium-coated polyurethane acrylate (PUA) pyramidal microstructures was illuminated by a traditional Ultraviolet (UV) lamp to generate an array of massive UV beam pens for realizing apertureless beam pen lithography. Experimental results reveal that significant UV energy can pass through the apex of a fully metal-coated PUA pyramid even though the thickness of the metallic coating exceeded the penetration depth. The patterned photoresist profiles were 117 nm deep and the full-width-at-half-magnitude (FWHM) was 180 nm when the exposure dosage was 54 mJ/cm(2) and the wavelength was 365 nm. Both depth and FWHM increased with exposure dosage, implying that the profiles depended on exposure dosage rather than on physical imprinting. With the adjustment of the thickness of the photoresist layer and the exposure parameters, the lift-off process yields arrayed metal dots with a diameter of 300 nm. Finite-element simulation of the intensity distribution near the apex of the pyramid and within the photoresist layer was carried out to reveal that the energy concentration within the pyramids is increased by approximately an order of magnitude, significantly enhancing the UV energy that passes through the fully metal-coated apex. The contrast curve model of the photoresist was used to calculate the patterned photoresist profiles for various energies. Experimental results, theoretical analysis and potential improvements of the method are presented.

Measurement of cylindrical Rayleigh surface waves using line-focused PVDF transducers and defocusing measurement method.

Line-focused PVDF transducers and defocusing measurement method are applied in this work to determine the dispersion curve of the Rayleigh-like surface waves propagating along the circumferential direction of a solid cylinder. Conventional waveform processing method has been modified to cope with the non-linear relationship between phase angle of wave interference and defocusing distance induced by a cylindrically curved surface. A cross correlation method is proposed to accurately extract the cylindrical Rayleigh wave velocity from measured data. Experiments have been carried out on one stainless steel and one glass cylinders. The experimentally obtained dispersion curves are in very good agreement with their theoretical counterparts. Variation of cylindrical Rayleigh wave velocity due to the cylindrical curvature is quantitatively verified using this new method. Other potential applications of this measurement method for cylindrical samples will be addressed.

Photolithographic patterning at sub-micrometer scale using a three-dimensional soft photo-mask with application on localized surface plasma resonance.

This paper presents a new method for fabricating arrayed metallic nano-structures with sub-micrometer line-widths over large patterning area sizes. It utilizes a soft mold containing arrayed surface micro-pyramids. A carbon-black photo-resist (PR) coating method is developed which can convert the soft mold into a photo-mask. This three-dimensional photo-mask is then applied for photolithographic ultraviolet (UV) patterning. In conjunction with standard metal lift-off process, arrayed metallic nano-structures are formed on glass substrates. A finite element simulation software is used to analyze the underlying mechanism of UV patterning using this new type of 3D photo-mask. The localized surface plasma resonance (LSPR) effects of the fabricated nano-structures are investigated both experimentally and theoretically. Good agreements are observed.

Fabrication of broadband poly(vinylidene difluoride-trifluroethylene) line-focus ultrasonic transducers for surface acoustic wave measurements of anisotropy of a (100) silicon wafer.

This paper investigates a new method for fabrication of broadband line-focus ultrasonic transducers by sol-gel spin-coating the poly(vinylidene difluoride-trifluroethylene) [P(VDF-TrFE)] copolymer film on a concave fine-polished beryllium copper backing. The ferroelectric hysteresis loops of the P(VDF-TrFE) films spin-coated from different molar ratios of VDF/TrFE, 77/23 and 55/45, were measured to select the better mixture. Owing to the better acoustic matching to water, compared with lead zirconate titanate (PZT), the fabricated transducers show relatively wide bandwidth of approximately 50 MHz with high central frequency of 60 MHz obtained at the focal plane when a fused-quartz acts as a reflecting target. Each one of the two finished transducers has a focal length of 5mm and a full aperture angle of 90°. After applying the specially developed digital signal processing algorithm to the defocusing experiment data, which is called V(f,z) analysis method based on two-dimensional fast Fourier transform (2-D FFT), the operating frequency can extend from several MHz to over 90 MHz. Surface acoustic wave (SAW) velocities of a typical (100) silicon wafer was measured along various directions between [100] and [010] to represent the anisotropic features.

Microwell chips for selection of bio-macromolecules that increase the differentiation capacities of mesenchymal stem cells.

Microwell chips (25 mm × 25 mm) are fabricated to select proper substrates for growing three-dimensional (3D) spheroids from mesenchymal stem cells (MSCs). Different bio-macromolecules and their combinations are immobilized on the chip by air plasma treatment and by polyelectrolyte interaction. Only a small number of MSCs (≈10(5) ) are needed for each chip. The expression level of N-cadherin, a cell-adhesion molecule, is used as an indicator for cell-cell interactions. MSC spheroids expressing the highest N-cadherin level also show the greatest osteogenic potential. The microwell chip may be used as an efficient platform to screen bio-macromolecules that enhance the differentiation potential of MSCs.

Fabrication of arrayed metallic nano-particles on a flexible substrate for inducing localized surface plasmon resonance.

This paper presents a new method for fabricating periodic arrays of metallic nano-particles on flexible substrates. This method is based on metallic film contact transfer method and high-power pulsed laser annealing. Experiments have been carried out to produce arrayed metallic nano-particles oriented in a hexagonal pattern. The nano-particle size is 70 nm in diameter and the center-to-center pitch of the hexagonal array is 400 nm. Large-area patterning and fabrication of these arrayed nano-particles can be easily achieved up to an area size of few cm(2). Besides, composite or compounded metallic nano-particle arrays can also be produced using different metal materials. The localized surface plasmon resonance (LSPR) effects induced by the fabricated arrays of nano-particles are experimentally observed and quantitatively measured. Numerical simulation on these LPSR effects is performed and the simulation results are in good agreement with experimental data.

Excimer laser micromachining of aspheric microlens arrays based on optimal contour mask design and laser dragging method.

This paper presents an improved excimer laser micromachining method for fabricating arrayed microstructures with a predesigned surface profile. The proposed method is developed from a conventional biaxial laser dragging method, but numerical analysis and optimal pattern design on the contour mask are introduced so that the machined surface profiles can be well controlled and matched to the designed profiles. To demonstrate the capability of this new approach, an array of aspheric microlenses that have analog surfaces for minimizing the focal spot sizes of the lenses is designed and fabricated. An array of 10×10 microlenses with an aperture size of 100 µm and a designed aspheric profile are obtained experimentally. The machined surface profiles are closely matched to their designed ones, with a profile deviation of less than 1 µm. Furthermore, the machined surfaces are smooth, with an average surface roughness of around 2 nm. Optical measurements on these machined aspheric microlenses show minimized focal spot sizes approaching their optical diffraction limits.

Laser ultrasonic evaluation of human dental enamel during remineralization treatment.

In this work a non-destructive laser ultrasonic technique is used to quantitatively evaluate the progressive change in the elastic response of human dental enamel during a remineralization treatment. The condition of the enamel was measured during two weeks treatment using laser generated and detected surface acoustic waves in sound and demineralized enamel. Analysis of the acoustic velocity dispersion confirms the efficacy, as well as illuminating the progress, of the treatment.

Serum globotriaosylceramide assay as a screening test for fabry disease in patients with ESRD on maintenance dialysis in Korea.

BACKGROUND/AIMS: Fabry disease is an X-linked recessive and progressive disease caused by α-galactosidase A (α-GaL A) deficiency. We sought to assess the prevalence of unrecognized Fabry disease in dialysis-dependent patients and the efficacy of serum globotriaosylceramide (GL3) screening. METHODS: A total of 480 patients of 1,230 patients among 17 clinics were enrolled. Serum GL3 levels were measured by tandem mass spectrometry. Additionally, we studied the association between increased GL3 levels and cardiovascular disease, cerebrovascular disease, or left ventricular hypertrophy. RESULTS: Twenty-nine patients had elevated serum GL3 levels. The α-GaL A activity was determined for the 26 patients with high GL3 levels. The mean α-GaL A activity was 64.6 nmol/hr/mg (reference range, 45 to 85), and no patient was identified with decreased α-GaL A activity. Among the group with high GL3 levels, 15 women had a α-GaL A genetics analysis. No point mutations were discovered among the women with high GL3 levels. No correlation was observed between serum GL3 levels and α-GaL A activity; the Pearson correlation coefficient was 0.01352 (p = 0.9478). No significant correlation was observed between increased GL3 levels and the frequency of cardiovascular disease or cerebrovascular disease. CONCLUSIONS: Fabry disease is very rare disease in patients with end-stage renal disease. Serum GL3 measurements as a screening method for Fabry disease showed a high false-positive rate. Thus, serum GL3 levels determined by tandem mass spectrometry may not be useful as a screening method for Fabry disease in patients with end stage renal disease.