Broadband frequency comb generation through cascaded quadratic nonlinearity in thin-film lithium niobate microresonators.

Broadband frequency comb generation through cascaded quadratic nonlinearity remains experimentally untapped in free-space cavities with bulk χ(2) materials mainly due to the high threshold power and restricted ability of dispersion engineering. Thin-film lithium niobate (LN) is a good platform for nonlinear optics due to the tight mode confinement in a nano-dimensional waveguide, the ease of dispersion engineering, large quadratic nonlinearities, and flexible phase matching via periodic poling. Here we demonstrate broadband frequency comb generation through dispersion engineering in a thin-film LN microresonator. Bandwidths of 150 nm (80 nm) and 25 nm (12 nm) for center wavelengths at 1560 and 780 nm are achieved, respectively, in a cavity-enhanced second-harmonic generation (doubly resonant optical parametric oscillator). Our demonstration paves the way for pure quadratic soliton generation, which is a great complement to dissipative Kerr soliton frequency combs for extended interesting nonlinear applications.

A colonial serrated polyp classification model using white-light ordinary endoscopy images with an artificial intelligence model and TensorFlow chart.

In this study, we implemented a combination of data augmentation and artificial intelligence (AI) model-Convolutional Neural Network (CNN)-to help physicians classify colonic polyps into traditional adenoma (TA), sessile serrated adenoma (SSA), and hyperplastic polyp (HP). We collected ordinary endoscopy images under both white and NBI lights. Under white light, we collected 257 images of HP, 423 images of SSA, and 60 images of TA. Under NBI light, were collected 238 images of HP, 284 images of SSA, and 71 images of TA. We implemented the CNN-based artificial intelligence model, Inception V4, to build a classification model for the types of colon polyps. Our final AI classification model with data augmentation process is constructed only with white light images. Our classification prediction accuracy of colon polyp type is 94%, and the discriminability of the model (area under the curve) was 98%. Thus, we can conclude that our model can help physicians distinguish between TA, SSA, and HPs and correctly identify precancerous lesions such as TA and SSA.

Gate-tunable frequency combs in graphene-nitride microresonators.

Optical frequency combs, which emit pulses of light at discrete, equally spaced frequencies, are cornerstones of modern-day frequency metrology, precision spectroscopy, astronomical observations, ultrafast optics and quantum information1-7. Chip-scale frequency combs, based on the Kerr and Raman nonlinearities in monolithic microresonators with ultrahigh quality factors8-10, have recently led to progress in optical clockwork and observations of temporal cavity solitons11-14. But the chromatic dispersion within a laser cavity, which determines the comb formation15,16, is usually difficult to tune with an electric field, whether in microcavities or fibre cavities. Such electrically dynamic control could bridge optical frequency combs and optoelectronics, enabling diverse comb outputs in one resonator with fast and convenient tunability. Arising from its exceptional Fermi-Dirac tunability and ultrafast carrier mobility17-19, graphene has a complex optical dispersion determined by its optical conductivity, which can be tuned through a gate voltage20,21. This has brought about optoelectronic advances such as modulators22,23, photodetectors 24 and controllable plasmonics25,26. Here we demonstrate the gated intracavity tunability of graphene-based optical frequency combs, by coupling the gate-tunable optical conductivity to a silicon nitride photonic microresonator, thus modulating its second- and higher-order chromatic dispersions by altering the Fermi level. Preserving cavity quality factors up to 106 in the graphene-based comb, we implement a dual-layer ion-gel-gated transistor to tune the Fermi level of graphene across the range 0.45-0.65 electronvolts, under single-volt-level control. We use this to produce charge-tunable primary comb lines from 2.3 terahertz to 7.2 terahertz, coherent Kerr frequency combs, controllable Cherenkov radiation and controllable soliton states, all in a single microcavity. We further demonstrate voltage-tunable transitions from periodic soliton crystals to crystals with defects, mapped by our ultrafast second-harmonic optical autocorrelation. This heterogeneous graphene microcavity, which combines single-atomic-layer nanoscience and ultrafast optoelectronics, will help to improve our understanding of dynamical frequency combs and ultrafast optics.

Association between adhesive capsulitis and thyroid disease: a meta-analysis.

HYPOTHESIS: Adhesive capsulitis (AC) is a common clinical condition of the shoulders without a clear pathophysiology or etiology. Although thyroid disease has been linked to AC, an appropriate understanding of the disease and its epidemiological evidence are lacking. This metaanalysis investigated the association of AC with thyroid disease and identified which manifestations of thyroid disease contribute to the risk of AC. MATERIALS AND METHODS: The databases of PubMed, Embase, and Scopus were searched for literature retrieval up to September 20, 2022. Articles evaluating the association between AC and any type of thyroid disease were enrolled. Data from studies reporting the prevalence and its 95% confidence interval (CI) were pooled. Subgroup analysis was performed on the different manifestations of thyroid disease. We explored heterogeneity with sensitivity analyses and publication bias with funnel plots and Egger's tests. A trim and fill analysis was conducted if publication bias was found. RESULTS: Results: In total, 10 case-control studies comprising a total of 127,967 patients were included. The prevalence of thyroid disease was significantly higher in patients with AC (odds ratio [OR] = 1.87, 95% CI: 1.37-2.57, P < .0001) than in patients without AC. The results of subgroup analysis indicated significantly higher rates of hypothyroidism (OR = 1.92, 95% CI: 1.09-3.39, P = .02) and subclinical hypothyroidism (OR = 2.56, 95% CI: 1.81-3.63, P < .00001), but not hyperthyroidism (OR = 1.42, 95% CI: 0.63-3.22, P = .40), among patients with AC than among those without AC. CONCLUSIONS: Our meta-analysis demonstrated that thyroid disease, especially when presenting as hypothyroidism or subclinical hypothyroidism, is associated with an increased risk of AC. Evidence for an association between hyperthyroidism and AC was not found, although this may be due to the lack of related studies. Further research on the pathogeneses of and relationship between these two diseases is warranted.

Association of Coffee and Tea Intake with Bone Mineral Density and Hip Fracture: A Meta-Analysis.

Background and Objectives: Osteoporosis is characterized by low bone mass and high bone fragility. Findings regarding the association of coffee and tea intake with osteoporosis have been inconsistent. We conducted this meta-analysis to investigate whether coffee and tea intake is associated with low bone mineral density (BMD) and high hip fracture risk. Materials and Methods: PubMed, MEDLINE, and Embase were searched for relevant studies published before 2022. Studies on the effects of coffee/tea intake on hip fracture/BMD were included in our meta-analysis, whereas those focusing on specific disease groups and those with no relevant coffee/tea intake data were excluded. We assessed mean difference (MD; for BMD) and pooled hazard ratio (HR; for hip fracture) values with 95% confidence interval (CI) values. The cohort was divided into high- and low-intake groups considering the thresholds of 1 and 2 cups/day for tea and coffee, respectively. Results: Our meta-analysis included 20 studies comprising 508,312 individuals. The pooled MD was 0.020 for coffee (95% CI, -0.003 to 0.044) and 0.039 for tea (95% CI, -0.012 to 0.09), whereas the pooled HR was 1.008 for coffee (95% CI, 0.760 to 1.337) and 0.93 for tea (95% CI, 0.84 to 1.03). Conclusions: Our meta-analysis results suggest that daily coffee or tea consumption is not associated with BMD or hip fracture risk.

Monostable dissipative Kerr solitons.

Kerr microcombs hold the promise of bringing frequency combs onto the chip and into a variety of applications requiring low size, weight, power, and cost. However, reliable Kerr microcomb generation is hindered by the thermal effect and multistability of dissipative Kerr solitons (DKSs). Past approaches toward Kerr microcomb reliability include either deterministic single-soliton generation or self-starting soliton behavior but not both. Here we describe a regime of DKSs that is both deterministic and self-starting, in which only a single soliton can stably exist. We term this new DKS regime "monostable DKSs" (MS-DKSs) as all other optical behaviors, such as continuous-wave-only and multiple solitons, are fundamentally forbidden by the design. We establish a graphical model to describe MS-DKSs and discuss the design principles of MS-DKSs. We numerically demonstrate the MS-DKS behavior in an example periodically poled lithium niobate microring resonator.

Inverse Relationship between Mean Corpuscular Volume and T-Score in Chronic Dialysis Patients.

Background and Objectives: Osteoporosis and anemia are prevalent among chronic kidney disease stage 5D (CKD stage 5D) patients. Osteoblasts are known as the niche cells of hematopoietic stem cells (HSCs) and stimulate HSCs to form blood-cell lineages within bone marrow microenvironments. We hypothesized that an inverse correlation may exist between mean corpuscular volume (MCV), a surrogate for ineffective hematopoiesis, and bone mineral density (BMD) in the CKD stage 5D population. Materials and Methods: This is a cross-sectional designed cohort study evaluating CKD stage 5D patients who have received dialysis therapy for over three months. Baseline clinical characteristics and laboratory data were prospectively collected. The dual-energy X-ray absorptiometry (DXA) method was used to measure BMD at five sites, which were bilateral femoral neck, total hip, and lumbar spine 1-4. The Pearson correlation test was initially adopted, and a multivariate linear regression model was further applied for potential confounder adjustments. Results: From September 2020 to January 2021, a total of 123 CKD stage 5D patients were enrolled. The Pearson correlation test revealed a significant inverse association between MCV and BMD at bilateral femoral neck and lumbar spine. The lowest T-score of the five body sites was determined as the recorded T-score. After adjustments for several potential confounding factors, the multivariate linear regression model found consistent negative associations between T-score and MCV. Conclusions: The present study found significant inverse correlations between MCV and BMD at specific body locations in patients on dialysis. A decreased T-score was also found to be associated with macrocytosis after adjustments for confounding variables. However, direct evidence for the causative etiology was lacking.

Multipronged Programmatic Strategy for Preventing Secondary Fracture and Facilitating Functional Recovery in Older Patients after Hip Fractures: Our Experience in Taipei Municipal Wanfang Hospital.

Background and Objectives: The study assessed the effectiveness of a fracture liaison service (FLS) after 1 year of implementation in improving the outcomes of hip fracture surgery in older adult patients at Taipei Municipal Wanfang Hospital. Materials and Methods: The Wanfang hospital's FLS program was implemented using a multipronged programmatic strategy. The aims were to encourage the screening and treatment of osteoporosis and sarcopenia, to take a stratified care approach for patients with a high risk of poor postoperative outcomes, and to offer home visits for the assessment of environmental hazards of falling, and to improve the patient's adherence to osteoporosis treatment. The clinical data of 117 and 110 patients before and after FLS commencement, respectively, were collected from a local hip fracture registry; the data were analyzed to determine the outcomes 1 year after hip fracture surgery in terms of refracture, mortality, and activities of daily living. Results: The implementation of our FLS significantly increased the osteoporosis treatment rate after hip fracture surgery from 22.8% to 72.3%, significantly decreased the 1-year refracture rate from 11.8% to 4.9%, non-significantly decreased 1-year mortality from 17.9% to 11.8%, and improved functional outcomes 1 year after hip fracture surgery. Conclusions: Implementation of our FLS using the multipronged programmatic strategy effectively improved the outcomes and care quality after hip fracture surgery in the older adult population, offering a successful example as a valuable reference for establishing FLS to improve the outcomes in vulnerable older adults.

In vitro and in vivo activities of imipenem combined with BLI-489 against class D ß-lactamase-producing Acinetobacter baumannii.

BACKGROUND: According to our preliminary study, BLI-489 has the potential to inhibit the hydrolysing activity of OXA-51-like ß-lactamase produced by carbapenem-resistant Acinetobacter baumannii (CRAb). OBJECTIVES: In the present study, the in vitro and in vivo activities of imipenem combined with BLI-489 against CRAb producing carbapenem-hydrolysing class D ß-lactamases (CHDLs), namely OXA-23, OXA-24, OXA-51 and OXA-58, were determined. METHODS: A chequerboard analysis of imipenem and BLI-489 was performed using 57 and 7 clinical CRAb isolates producing different CHDLs and MBLs, respectively. Four representative strains harbouring different CHDL genes were subjected to a time-kill assay to evaluate the synergistic effects. An in silico docking analysis was conducted to simulate the interactions between BLI-489 and the different families of CHDLs. The in vivo activities of this combination were assessed using a Caenorhabditis elegans survival assay and a mouse pneumonia model. RESULTS: Chequerboard analysis showed that imipenem and BLI-489 had a synergistic effect on 14.3, 92.9, 100, 16.7 and 100% of MBL-, OXA-23-, OXA-24-like-, OXA-51-like- and OXA-58-producing CRAb isolates, respectively. In the time-kill assay, imipenem and BLI-489 showed synergy against OXA-24-like-, OXA-51-like- and OXA-58-, but not OXA-23-producing CRAb isolates after 24 h. The in silico docking analysis showed that BLI-489 could bind to the active sites of OXA-24 and OXA-58 to confer strong inhibition activity. The combination of imipenem and BLI-489 exhibited synergistic effects for the rescue of CRAb-infected C. elegans and mice. CONCLUSIONS: Imipenem combined with BLI-489 has synergistic effects against CHDL-producing CRAb isolates.

Midinfrared Tunable Laser with Noncritical Frequency Matching in Box Resonator Geometry.

Monolithic optical parametric oscillators extend laser frequencies in compact architectures, but normally guide and circulate all pump, signal, and idler beams. Critical frequency matching is raised among these resonances, limiting operation stability and continuous tuning. Here, we develop a box resonator geometry that guides all beams but only resonates for signal. Such noncritical frequency matching enables 227 GHz continuous tuning, with sub-10 kHz linewidth and 0.43 W power at 3310 nm. Our results confirm that monolithic resonator can be effectively used as a tunable laser including midinfrared wavelength, as further harnessed with methane fine spectral measurement at MHz accuracy.

Symbiotic quadratic soliton mode-locked non-degenerate optical parametric oscillators.

We analytically and numerically unveil the existence condition of symbiotic solitons in doubly resonant non-degenerate optical parametric oscillators. Resonant signal and idler with terahertz comb bandwidth and femtosecond pulse duration in the mid-infrared are attainable through this symbiotic soliton mode-locking technique. The group velocity mismatches between the three interacting waves are the dominant cause of the symbiotic soliton perturbation, and their effects are numerically investigated in detail. The principle can be applied to commonly used mid-infrared material platforms, making it a competitive ultrashort pulse and broadband comb source architecture.

Quadratic soliton mode-locked degenerate optical parametric oscillator.

We examine the existence condition of the quadratic soliton mode-locked degenerate optical parametric oscillator in the previously unexplored parameter space. We study the nature of the quadratic solitons and divide their dynamics into two distinctive branches, depending on the system parameters. Origin of the quadratic soliton perturbation is identified, and strategy to mitigate its detrimental effect is developed. Frequency comb with terahertz bandwidth and femtosecond pulse duration are attainable in an example periodically poled lithium niobate waveguide resonator. Design rules of the quadratic soliton mode-locking are summarized. The principle can be further extended to other material platforms, making it a competitive ultrashort pulse and broadband comb source architecture at the mid-infrared.

Photonic Flywheel in a Monolithic Fiber Resonator.

We demonstrate the first compact photonic flywheel with sub-fs time jitter (averaging times up to 10 µs) at the quantum-noise limit of a monolithic fiber resonator. Such quantum-limited performance is accessed through novel two-step pumping scheme for dissipative Kerr soliton generation. Controllable interaction between stimulated Brillouin lasing and Kerr nonlinearity enhances the DKS coherence and mitigates the thermal instability challenge, achieving a remarkable 22-Hz intrinsic comb linewidth and an unprecedented phase noise of -180 dBc/Hz at 945-MHz carrier at free running. The scheme can be generalized to various device platforms for field-deployable precision metrology.

A Dynamic Hanging-Drop System for Mesenchymal Stem Cell Culture.

There have been many microfluid technologies combined with hanging-drop for cell culture gotten developed in the past decade. A common problem within these devices is that the cell suspension introduced at the central inlet could cause a number of cells in each microwell to not regularize. Also, the instability of droplets during the spheroid formation remains an unsolved ordeal. In this study, we designed a microfluidic-based hanging-drop culture system with the design of taper-tube that can increase the stability of droplets while enhancing the rate of liquid exchange. A ring is surrounding the taper-tube. The ring can hold the cells to enable us to seed an adequate amount of cells before perfusion. Moreover, during the period of cell culture, the mechanical force around the cell is relatively low to prevent stem cells from differentiate and maintain the phenotype. As a result of our hanging system design, cells are designed to accumulate at the bottom of the droplet. This method enhances convenience for observation activities and analysis of experiments. Thus, this microfluid chip can be used as an in vitro platform representing in vivo physiological conditions, and can be useful in regenerative therapy.

Three-Dimensional Printed Porous Titanium Screw with Bioactive Surface Modification for Bone-Tendon Healing: A Rabbit Animal Model.

The interference screw fixation method is used to secure a graft in the tibial tunnel during anterior cruciate ligament reconstruction surgery. However, several complications have been reported, such as biodegradable screw breakage, inflammatory or foreign body reaction, tunnel enlargement, and delayed graft healing. Using additive manufacturing (AM) technology, we developed a titanium alloy (Ti6Al4V) interference screw with chemically calcium phosphate surface modification technology to improve bone integration in the tibial tunnel. After chemical and heat treatment, the titanium screw formed a dense apatite layer on the metal surface in simulated body fluid. Twenty-seven New Zealand white rabbits were randomly divided into control and additive manufactured (AMD) screw groups. The long digital extensor tendon was detached and translated into a tibial plateau tunnel (diameter: 2.0 mm) and transfixed with an interference screw while the paw was in dorsiflexion. Biomechanical analyses, histological analyses, and an imaging study were performed at 1, 3, and 6 months. The biomechanical test showed that the ultimate pull-out load failure was significantly higher in the AMD screw group in all tested periods. Micro-computed tomography analyses revealed early woven bone formation in the AMD screw group at 1 and 3 months. In conclusion, AMD screws with bioactive surface modification improved bone ingrowth and enhanced biomechanical performance in a rabbit model.

Synthesis of Fluorescent Carbon Dots as Selective and Sensitive Probes for Cupric Ions and Cell Imaging.

A novel sensing system has been designed for the detection of cupric ions. It is based on the quenched fluorescence signal of carbon dots (CDs), which were carbonized from poly(vinylpyrrolidone) (PVP) and L-Cysteine (CYS). Cupric ions interact with the nitrogen and sulfur atoms on surface of the CDs to form an absorbed complex; this results in strong quenching of the fluorescence of the CDs via a fast metal-to-ligand binding affinity. The synthesized water-soluble CDs also exhibited a quantum yield of 7.6%, with favorable photoluminescent properties and good photostability. The fluorescence intensity of the CDs was very stable in high ionic strength (up to 1.0 M NaCl) and over a wide range of pH levels (2.0-12.0). This facile method can therefore develop a sensor that offers reliable, fast, and selective detection of cupric ions with a detection limit down to 0.15 µM and a linear range from 0.5 to 7.0 µM (R2 = 0.980). The CDs were used for cell imaging, observed that they were low toxicity to Tramp C1 cells and exhibited blue and green and red fluorescence under a fluorescence microscope. In summary, the CDs exhibited excellent fluorescence properties, and could be applied to the selective and sensitive detection of cupric ion and multicolor cell imaging.

Terabit optical OFDM superchannel transmission via coherent carriers of a hybrid chip-scale soliton frequency comb.

We demonstrate seamless channel multiplexing and high bitrate superchannel transmission of coherent optical orthogonal frequency division multiplexing (CO-OFDM) data signals utilizing a dissipative Kerr soliton (DKS) frequency comb generated in an on-chip microcavity. Aided by comb line multiplication through Nyquist pulse modulation, the high stability and mutual coherence among mode-locked Kerr comb lines are exploited for the first time, to the best of our knowledge, to eliminate the guard intervals between communication channels and achieve full spectral density bandwidth utilization. Spectral efficiency as high as 2.625 bit/Hz/s is obtained for 180 CO-OFDM bands encoded with 12.75 Gbaud 8-QAM data, adding to the total bitrate of 6.885 Tb/s within a 2.295 THz frequency comb bandwidth. This Letter confirms that high coherence is the key superiority of Kerr soliton frequency combs over independent laser diodes, as a multi-spectral coherent laser source for high-bandwidth high-spectral-density transmission networks.

Graphene-Enhanced Brillouin Optomechanical Microresonator for Ultrasensitive Gas Detection.

Chemical sensing is one of the most important applications of nanoscience, whose ultimate aim is to seek higher sensitivity. In recent years, graphene with intriguing quantum properties has spurred dramatic advances ranging from materials science to optoelectronics and mechanics, showing its potential to realize individual molecule solid-state sensors. However, for optical sensing the single atom thickness of graphene greatly limits the light-graphene interactions, bottlenecking their performances. Here we demonstrate a novel approach based on the forward phase-matched Brillouin optomechanics in a graphene inner-deposited high Q (>2 × 106) microfluidic resonator, expanding the "electron-photon" interaction in conventional graphene optical devices to the "electron-phonon-photon" process. The molecular adsorption induced surface elastic modulation in graphene enables the Brillouin optomechanical modes (mechanical Q ≈ 43,670) extremely sensitive (200 kHz/ppm) in ammonia gas detection, achieving a noise equivalent detection limit down to 1 ppb and an unprecedented dynamic range over five orders-of-magnitude with fast response. This work provides a new platform for the researches of graphene-based optomechanics, nanophotonics, and optical sensing.

Quasi-phase-matched multispectral Kerr frequency comb.

We study a new type of Kerr frequency comb where the momentum conservation law is fulfilled by azimuthal modulation of the waveguide dispersion. The concept can expand the parametric range in which a Kerr frequency comb is obtained. In a good agreement with the theoretical analysis, we demonstrate a multispectral Kerr frequency comb covering important fiber-optic communication bands. Comb coherence and absence of a sub-comb offset are confirmed by continuous-wave heterodyne beat note and amplitude noise spectra measurements. The device can be used for achieving broadband optical frequency synthesizers and high-capacity coherent communication.

Microresonator-stabilized extended-cavity diode laser for supercavity frequency stabilization.

We demonstrate a simple, compact, and cost-effective laser noise reduction method for stabilizing an extended-cavity diode laser to a 3×105 finesse mirror Fabry-Perot (F-P) cavity, corresponding to a resonance linewidth of 10 kHz, by using a crystalline MgF2 whispering gallery mode microresonator. The laser linewidth is reduced to sub-kilohertz such that a stable Pound-Drever-Hall error signal is built up. The wavelength of the pre-stabilized laser is tunable within a large bandwidth covering the high-reflection mirror coating of an F-P supercavity.