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PURPOSE: Few studies have investigated the factors associated with ambulation and survival over one year. Therefore, this study aimed to examine the factors that influence ambulation and survival rates in elderly patients who have undergone conservative management for hip fractures. MATERIALS AND METHODS: This retrospective study included 74 ambulatory individuals aged 65 years or older prior to their injuries. One-year mortality and ambulatory status were assessed. Statistical comparisons of background and medical characteristics between groups of independent and non-independent walkers, as well as between survivors and mortalities, were performed using the Pearson chi-squared, Fisher exact, and Mann-Whitney U tests. RESULTS: The numbers of older patients able to walk independently, those not able to walk independently, and those with mortality at one-year post-injury after conservative management of hip fractures were 13 (18.3%), 35 (49.3%), and 23 (32.4%), respectively. Independent walkers one year after conservative treatment for hip fracture were younger (p=0.04) and less likely to have cognitive impairment (p=0.04) than non-independent walkers. The proportion of individuals with cognitive impairment was found to be lower among survivors than among mortalities (p=0.0098). CONCLUSION: Cognitive decline may contribute to difficulties in walking independently and mortality at one year post-injury in this population.
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Digital therapeutics (DTx) in hearing research have emerged as a new category of therapies providing evidence-based intervention via digital means, such as software, smartphone apps, or websites. However, although relatively new, they are not well-established. In this article, we review DTx technologies in hearing research fields, focusing on three categories: prevention and diagnosis, aid (assistance), and cure (digital medicine). We observe that most DTx systems require interactions with users (or patients) without the direct support of clinical professionals to obtain or collect medical evidence; this makes training (or education) features crucial to the therapy's success. In this view, this article discusses the education or training functions of the current DTx and their contribution and purposes. The impact of emerging artificial intelligence (AI) on DTx in hearing research is being explored, and the future of DTx concerning AI integration is being discussed. We believe that this work will contribute to a better understanding of the current and future DTx technological advancements and, in particular, shed light on the field of hearing research.
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With dental implant treatment becoming the gold standard, the need for effective bone augmentation prior to implantation has grown. This study aims to evaluate a bone augmentation strategy integrating three key growth factors: bone morphogenetic protein-2 (BMP-2), insulin-like growth factor 1 (IGF-1), and vascular endothelial growth factor (VEGF). Collagen scaffolds incorporating BMP-2, IGF-1, or VEGF were fabricated and categorized into five groups based on their content: scaffold alone; BMP-2 alone (BMP-2); BMP-2 and IGF-1 (BI); BMP-2, IGF-1, and VEGF (BIV); and BMP-2 and IGF-1 with an earlier release of VEGF (BI + V). The prepared scaffolds were surgically implanted into the calvarias of C57BL/6JJcl mice, and hard tissue formation was assessed after 10 and 28 days through histological, tomographic, and biochemical analyses. The combination of BMP-2 and IGF-1 induced a greater volume of hard tissue augmentation compared with that of BMP-2 alone, regardless of VEGF supplementation, and these groups had increased levels of cartilage compared with others. The volume of hard tissue formation was greatest in the BIV group. In contrast, the BI + V group exhibited a hard tissue volume similar to that of the BI group. While VEGF and CD31 levels were highest in the BIV group at 10 days, there was no correlation at the same time point between hard tissue formation and the quantity of M2 macrophages. In conclusion, the simultaneous release of BMP-2, IGF-1, and VEGF proved to be effective in promoting bone augmentation.
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Proteína Morfogenética Óssea 2 , Fator de Crescimento Insulin-Like I , Fator A de Crescimento do Endotélio Vascular , Animais , Proteína Morfogenética Óssea 2/farmacologia , Camundongos , Fator de Crescimento Insulin-Like I/farmacologia , Fator de Crescimento Insulin-Like I/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/farmacologia , Alicerces Teciduais/química , Crânio/metabolismo , Camundongos Endogâmicos C57BL , MasculinoRESUMO
OBJECTIVES: This study aimed to determine the crystalline phase composition of 3-6 mol% yttria-stabilized zirconia (3-6YSZ), specifically investigating the presence of tetragonal (t), cubic (c), and/or additional yttria-rich tetragonal (t') phase. METHODS: Laboratory-fabricated specimens comprising 3-5YSZ, resembling translucent dental zirconia ceramics (TZ specimens), and a blend of 3YSZ and 8YSZ, representing a c-phase reference, were prepared. Additionally, 25 dental zirconia products stabilized with 3-6 mol% yttria were analyzed. Whole X-ray diffraction (XRD) patterns were obtained for Rietveld analysis, complemented by fine scanning in the 2θ region from 72º to 76º for qualitative phase analysis. Moreover, yttria concentrations in each specimen were determined using X-ray fluorescence (XRF) spectroscopy. RESULTS: In the 2θ region from 72º to 76º, TZ and dental zirconia product specimens displayed four peaks attributed to t- and t'-phases, but the c-phase peak was absent. Rietveld analysis of the whole XRD patterns, utilizing a t-t' model, demonstrated the t-phase fraction ranging from 86 mass% in 3YSZ to 11 mass% in 6YSZ. Rietveld analysis appeared reliable, as the yttria contents calculated based on lattice parameters aligned well with those measured by XRF. This study established that dental 3-6YSZ consisted of yttria-lean t- and yttria-rich t'-phases. SIGNIFICANCE: The present study enhances understanding of the crystalline structure of dental zirconia ceramics. Future crystallographic analyses of these ceramics should consider the presence of t- and t'-phases.
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Cerâmica , Teste de Materiais , Difração de Raios X , Ítrio , Zircônio , Zircônio/química , Ítrio/química , Cerâmica/química , Propriedades de Superfície , Espectrometria por Raios X , Cristalografia , Materiais Dentários/químicaRESUMO
BACKGROUND: Although an increasing number of network meta-analyses have been conducted on the effectiveness of conservative therapy for knee osteoarthritis, these may have been poorly planned and executed.We aimed to review the qualities of a comprehensive set of network meta-analyses on rehabilitation therapies for knee osteoarthritis and provide an overview of the effectiveness of each therapy. METHODS: The eligibility criteria were as follows: (i) conservative rehabilitation was the primary treatment in the intervention group, (ii) included patients were diagnosed with knee osteoarthritis, and (iii) patient groups were aged ≤75 years, and rehabilitation interventions comprised exercise, orthotic, or physical therapies or patient education. Two independent reviewers screened the titles and abstracts of the identified records and selected the eligible reviews; their full texts were further assessed for eligibility. Then, a checklist derived from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension statement for the reporting of systematic reviews incorporating network meta-analyses of healthcare Interventions was used to validate the completeness of the reporting of each network meta-analysis. Furthermore, the statistical and outcome data regarding the quality of life, knee joint function and pain, adverse events, and physical functions were extracted using a customized spreadsheet. RESULTS: Overall, 2701 titles and abstracts were screened, and eight network meta-analyses were ultimately selected. Nearly all reviews adequately addressed the PRISMA extension checklist, and the completeness of reporting was adequate; therefore, all expected information could be extracted. However, the methodology used to confirm the transitivity assumption was insufficient in many reviews. The following interventions were effective in reducing pain and improving physical function: (i) strengthening, flexibility, aerobic, and mind-body exercises, (ii) pulsed ultrasound, (iii) focused and radial extracorporeal shockwave therapy, and (iv) continuous ultrasound. The following interventions were effective in improving the quality of life: (i) strengthening, (ii) mixed, and (iii) mind-body exercises. CONCLUSIONS: Our results suggested that exercise therapies, including muscle-strengthening, aerobic, flexibility, and mind-body exercises, are likely to be effective for pain relief and functional improvement in knee osteoarthritis. This may be the first review to provide a comprehensive perspective for considering priorities for future rehabilitation interventions for knee osteoarthritis.
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Burning mouth syndrome (BMS) is a chronic oral pain disorder. There is a theory that BMS is a form of nociplastic pain. A standard treatment for BMS has not yet been established. Kampo medicine is a traditional oriental medicine. The purpose of this study is to evaluate the effectiveness of Rikkosan-a traditional Japanese herbal medicine (Kampo)-in the treatment of BMS. A single-center retrospective study was conducted on 20 patients who were diagnosed with BMS and treated with Rikkosan alone (total daily dose; 7.5 g) three times daily for approximately 4 weeks (29.5 ± 6.5 days). Rikkosan was dissolved in hot water and taken internally. They had an average age of 63 years, and 90% were being treated for other illnesses, but their medication status was the same during this study period, except for Rikkosan. No adverse events were observed in patients. Numerical rating scale (NRS) or visual analog scale (VAS)/10 scores decreased significantly between the time of the initiation of Rikkosan and one month after (-2.1 ± 1.2, p < 0.05). Rikkosan has a short-term effect of reducing NRS by two levels in BMS patients.
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Phage therapy has re-emerged in modern medicine as a robust antimicrobial strategy in response to the increasing prevalence of antimicrobial-resistant bacteria. However, bacterial resistance to phages can also arise via a variety of molecular mechanisms. In fact, several clinical studies on phage therapy have reported the occurrence of phage-resistant variants, representing a significant concern for the successful development of phage-based therapies. In this context, the fitness trade-offs between phage and antibiotic resistance have revealed new avenues in the field of phage therapy as a countermeasure against phage resistance. This strategy forces to restore the antibiotic susceptibility of antimicrobial-resistant bacteria as compensation for the development of phage resistance. Here, we present the key achievements of these fitness trade-offs, notably focusing on the enhancement of antibiotic sensitivity through the induction of large chromosomal deletions by bacteriophage infection. We also describe the challenges of this strategy that need to be overcome to promote favorable therapeutic outcomes and discuss future directions. The insights gained from the trade-offs between phage and antibiotic sensitivity will help maximize the potential of phage therapy for the treatment of infectious diseases.
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OBJECTIVES: Several studies have reported the effects of Fusobacterium nucleatum stimulation on oral cancer cells. However, given that these studies typically span a stimulation period of three days to eight days, the in vitro studies conducted to date may not fully mimic the oral cancer environment, which involves constant exposure to oral commensal bacteria. This study aimed to elucidate the effects of prolonged and persistent Fusobacterium nucleatum infection on oral cancer cells. METHODS: Human tongue squamous cell carcinoma (SCC) cells were continuously stimulated with Fusobacterium nucleatum for two or four weeks, then experimentally evaluated. RESULTS: Prolonged, persistent Fusobacterium nucleatum stimulation increased the cells' proliferative, invasive, and migratory capacities, decreased their expression of epithelial markers, and increased their expression of mesenchymal markers progressively with time. The cells also adopted a spindle-shaped morphology and cell-to-cell contact dependence was progressively lost, suggesting time-dependent occurrence of epithelial-mesenchymal transition. Furthermore, mRNA levels of CD44, a cancer stem cell marker, were time-dependently upregulated. When SCC cells were stimulated with Fusobacterium nucleatum for four weeks in the presence of dexamethasone, Fusobacterium nucleatum induced epithelial-mesenchymal transition was inhibited. CONCLUSIONS: Epithelial-mesenchymal transition in human tongue SCC cells was time-dependently induced by prolonged, persistent Fusobacterium nucleatum stimulation and inhibited by dexamethasone. Routine decontamination of the oral cavity may be crucial for controlling tumor invasion and metastasis.
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Carcinoma de Células Escamosas , Transição Epitelial-Mesenquimal , Fusobacterium nucleatum , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/microbiologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias Bucais/patologia , Neoplasias Bucais/microbiologia , Neoplasias da Língua/patologia , Neoplasias da Língua/microbiologia , Infecções por Fusobacterium/microbiologia , Infecções por Fusobacterium/patologia , Dexametasona/farmacologia , Receptores de Hialuronatos/metabolismo , Invasividade NeoplásicaRESUMO
The research exploiting the ability of dental materials to induce or prevent secondary caries (SC) development still seems inconclusive. Controlling bacterial adhesion by releasing bacteriostatic ions and improving the surface structure has been suggested to reduce the occurrence of SC. This paper analyses the impact of five distinctively composed dental materials on cariogenic biofilm formation. Forty-five specimens of three composites (CeramX Spectra ST, Admira Fusion, Beautifil II) and two glass-ionomers (Fuji II LC, Caredyne Restore), respectively, were incubated in bacterial suspension composed of Streptococcus mutans, Lactobacillus acidophilus, Streptococcus mitis, Streptococcus sanguinis, and Streptococcus salivarius at pH 7.0 and 5.5. Coverslips were used as a control. Adhered bacteria were collected after 2, 4, 6, 12, 24, and 48 h and analyzed using quantitative polymerase chain reaction (qPCR). Fluoride leakage was measured at each collection. The specimens' surface topography was assessed using interferometry. In the present study, surface roughness seemed to have a partial role in bacterial adhesion and biofilm formation, together with chemical composition of the materials tested. Despite differences in fluoride leakage, biofilm accumulation was similar across materials, but the number of adhered bacteria differed significantly. A release of other ions may also affect adhesion. These variations suggest that certain materials may be more prone to initiating secondary caries.
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An efficient method to prepare dibenzothiophene S-oxides is disclosed. Suzuki-Miyaura cross-coupling of 2-bromoaryl sulfinate esters with arylboronic acids selectively at the bromo group followed by electrophilic cyclization of the resulting sulfinate ester moiety provides diverse dibenzothiophene S-oxides. Further transformations including Pummerer-type C-H propargylation and aryne reactions realize to synthesize highly functionalized dibenzothiophene derivatives.
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The effect of terahertz (THz) radiation has been studied in medicine. However, there is a lack of scientific information regarding its possible mutagenicity. Therefore, the present study aimed to assess the mutagenicity of 1.6 THz laser irradiation. The Ames test was conducted using five bacterial tester strains. The bacteria were subjected to (i) 1.6 THz laser irradiation at 3.8 mW/cm2 for 60 min using a tabletop THz pulse laser system, (ii) ultraviolet irradiation, (iii) treatment with positive control chemicals (positive control) or (iv) treatment with the solvent used in the positive control (negative control). After treatment, the bacterial suspensions were cultured on minimal glucose agar to determine the number of revertant colonies. In addition, the comet assay was performed using fibroblasts (V79) to assess possible DNA damage caused by the THz laser irradiation. The Ames test demonstrated that the THz laser irradiation did not increase the number of revertant colonies compared to that in the negative control group, whereas the ultraviolet irradiation and positive control treatment increased the number of revertant colonies. Thus, 1.6 THz laser irradiation is unlikely to be mutagenic. The comet assay additionally suggests that the THz laser irradiation unlikely induce cellular DNA damage.
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Dano ao DNA , Mutagênicos , Mutagênicos/toxicidade , Ensaio Cometa , Mutagênese , Fibroblastos/efeitos da radiação , Testes de MutagenicidadeRESUMO
A polystyrene (PS) certified reference material (CRM) for the analysis of decabromodiphenyl ether (BDE 209) was issued. PS disk was prepared by injection molding of the mixture of versine PS and BDE 209. The certification of the PS CRM was conducted by two analytical methods with different sample preparation methods using isotope dilution mass spectrometry (IDMS). The certified value, wCRM, was 978 mg/kg, and this value coincided with the regulation value of BDE 209 in the Restriction of Hazardous Substances directive (1000 mg/kg). The uncertainties related to certification, uwmean, inhomogeneity, uhom, and long- and short-term instability, usts and ults, respectively, were evaluated based on the mass fraction of BDE 209. The uwmean, uhom, usts, and ults were 0.0265, 0.0046, 0.0061, and 0.0099 (relative), respectively, and the expanded uncertainty for this CRM was determined as 57 mg/kg (coverage factor is 2). Additionally, the quantitative capability of the thermal desorption-gas chromatography/mass spectrometry (TD-GC/MS) method was evaluated. In TD-GC/MS, the analytical values of the developed CRM obtained by the external and internal standard methods with matrix-free calibrants were out of the range of the wCRM (almost 10% larger or smaller), whereas those with matrix-matched calibrants agreed with the wCRM. In contrast to these results, the analytical values obtained by TD-GC/MS using IDMS were consistent with the wCRM no matter if matrix-free or matrix-matched calibrants were used. These results indicated that, for quantification of BDE 209 in PS, the trueness and precision of TD-GC/MS can be enhanced by applying IDMS without matrix-matched calibrants.
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A method of quantifying glyphosate (Gly) in human urine by means of MonoSpin TiO extraction and 9-fluorenylmethoxycarbonyl chloride (FMOC-Cl) derivatization with isotope dilution mass spectrometry (IDMS) was investigated and optimized. The method's quantification limit under optimized conditions was 0.3 µg/kg for FMOC-Gly, which was comparable to or lower than those described in previous studies. When a spike test using human urine samples was carried out with optimized analytical conditions, the trueness for FMOC-Gly was as follows: 101.6-104.9% for a spike level of 0.5 µg/kg and 99.2-101.0% for a spike level of 30 µg/kg. The intra-day repeatability and inter-day reproducibility were <6.5%. The spike test results for validation between the "with" and "without" derivatization methods were comparable at 1 µg/kg. Our results indicate that using MonoSpin TiO extraction and FMOC-Cl derivatization with IDMS is an accurate method for analyzing Gly in human urine.
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In recent decades, phage therapy has been overshadowed by the widespread use of antibiotics in Western countries. However, it has been revitalized as a powerful approach due to the increasing prevalence of antimicrobial-resistant bacteria. Although bacterial resistance to phages has been reported in clinical cases, recent studies on the fitness trade-offs between phage and antibiotic resistance have revealed new avenues in the field of phage therapy. This strategy aims to restore the antibiotic susceptibility of antimicrobial-resistant bacteria, even if phage-resistant variants develop. Here, we summarize the basic virological properties of phages and their applications within the context of antimicrobial resistance. In addition, we review the occurrence of phage resistance in clinical cases, and examine fitness trade-offs between phage and antibiotic sensitivity, exploring the potential of an evolutionary fitness cost as a countermeasure against phage resistance in therapy. Finally, we discuss future strategies and directions for phage-based therapy from the aspect of fitness trade-offs. This approach is expected to provide robust options when combined with antibiotics in this era of phage 're'-discovery.
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Infecções Bacterianas , Bacteriófagos , Terapia por Fagos , Humanos , Bacteriófagos/genética , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Terapia por Fagos/métodos , Infecções Bacterianas/terapia , BactériasRESUMO
Expression of concern for 'Versatile plasmonic-effects at the interface of inverted perovskite solar cells' by Ahmed Esmail Shalan, et al., Nanoscale, 2017, 9, 1229-1236, https://doi.org/10.1039/C6NR06741G.
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Developing a method for creating a novel catalysis of organic molecules is essential because of the growing interest in organocatalysis. In this study, we found that cyclic carbonates immobilized on a nonporous or mesoporous silica support showed catalytic activity for hydrosilylation, which was not observed for the free cyclic carbonates, silica supports, or their physical mixture. Analysis of the effects of linker lengths and pore sizes on the catalytic activity and carbonate C=O stretching frequency revealed that the proximity of carbonates and surface silanols was crucial for synergistic hydrosilylation catalysis. A carbonate and silanol concertedly activated the silane and aldehyde for efficient hydride transfer. Density functional theory calculations on a model reaction system demonstrated that both the carbonate and silanol contributed to the stabilization of the transition state of hydride transfer, which resulted in a reasonable barrier height of 16.8 kcal mol-1. Furthermore, SiO2/carbonate(C4) enabled the hydrosilylation of an aldehyde with an amino group without catalyst poisoning, owing to the weak acidity of surface silanols, in sharp contrast to previously developed acid catalysts. This study demonstrates that immobilization on a solid support can convert inactive organic molecules into active and heterogeneous organocatalysts.
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Monolithic dental prostheses made of 3-6 mol% yttria-stabilized zirconia (3-6YSZ) have gained popularity owing to their improved material properties and semi-automated fabrication processes. In this study, we aimed to evaluate the influence of mechanical surface treatments, such as polishing, grinding, and sandblasting, on the residual stress of 3-6YSZ used for monolithic prostheses in association with crystalline phase transformation. Plate specimens were prepared from five dental zirconia blocks: Aadva Zirconia ST (3YSZ), Aadva Zirconia NT (6YSZ), Katana HT (4YSZ), Katana STML (5YSZ), and Katana UTML (6YSZ). The specimens were either polished using 1, 3, or 9 µm diamond suspensions, ground using 15, 35, or 55 µm diamond discs, or sandblasted at 0.2, 0.3, or 0.4 MPa. The residual stress, crystalline phase, and hardness were analyzed using the cosα method, X-ray diffraction (XRD), and Vickers hardness test, respectively. Additionally, we analyzed the residual stress on the surfaces of monolithic zirconia crowns (MZCs) made of 4YSZ, 5YSZ, and 6YSZ, which were processed using clinically relevant procedures, including manual grinding, followed by polishing using a dental electric motor on the external surface, and sandblasting on the internal surface. Residual stress analysis demonstrated that grinding and sandblasting, particularly the latter, resulted in the generation of compressive residual stress on the surfaces of the plate specimens. XRD revealed that the ground and sandblasted specimens contained a larger amount of the rhombohedral phase than that of the polished specimens, which may be a cause of the residual stress. Sandblasting significantly increased the Vickers hardness compared to polishing, which may possibly be due to the generation of compressive residual stress. In the case of MZCs, compressive residual stress was detected not only on the sandblasted surface, but also on the polished surface. The difference in the residual stress between the plate and crown specimens may be related to the force applied during the automated and manual grinding and polishing procedures. Further studies are required to elucidate the effects of the compressive residual stress on the clinical performance of MZCs.
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Ítrio , Zircônio , Teste de Materiais , Propriedades de Superfície , Zircônio/química , Ítrio/química , Cerâmica/química , Diamante , Materiais Dentários , Polimento Dentário , Estresse MecânicoRESUMO
A practical method to synthesize sulfinate esters from aryl iodides is disclosed. Direct oxidation of thioesters prepared by copper-catalyzed C-S formation of aryl iodides realized the efficient synthesis of sulfinate esters. Due to the good accessibility of aryl iodides, a wide variety of sulfinate esters were prepared from easily available starting materials such as carboxylic acids and anilines.
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BACKGROUND: Supercritical fluid extraction (SFE) is a fast, versatile, and solvent-efficient automatic extraction method. Despite its advantages, the results of our proficiency tests imply that the applicability assessments of SFE for pesticide residues were insufficient. OBJECTIVE: In this study, as analytical method using SFE was optimized and validated by testing the incurred and fortified brown rice samples with organophosphorus (OP), pyrethroid (PYR), and dithiolane (DIT) pesticides. METHOD: A validation study using the incurred sample with etofenprox, fenitrothion, and isoprothiolane was performed by comparing the analytical results obtained using the SFE and solid-liquid extraction with homogenization (SLE), which is a well-validated official multi-residue extraction method. The tests on the fortified samples were also performed for seven pesticide residues, chlorpyrifos, diazinon, O-ethyl O-4-nitrophenyl phenylphosphonothioate (EPN), etofenprox, fenitrothion, isoxathion, and isoprothiolane, at three fortification levels, 0.001, 0.01, and 0.1 mg/kg. RESULTS: In the test on the incurred samples, optimized SFE-to-SLE analytical values (CSFE/CSLE) were 99.2-100.1%, with RSD lower than 3%. In contrast, the analytical-to-spiked concentrations in the tests on the fortified samples were 96.4-105.0%, with RSD lower than 8.8%. CONCLUSIONS: These results indicate that the proposed SFE method, which is well validated with the incurred brown rice sample, is useful for determining OP, PYR, and DIT pesticide residues in brown rice. HIGHLIGHTS: The proposed SFE method satisfies EU and Japanese maximum residue limits (MRLs). The consumption of solvent can be reduced to one-fourth of that of SLE using the proposed SFE method.
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Cromatografia com Fluido Supercrítico , Oryza , Resíduos de Praguicidas , Piretrinas , Resíduos de Praguicidas/análise , Cromatografia com Fluido Supercrítico/métodos , Espectrometria de Massas em Tandem , Fenitrotion/análise , Piretrinas/análise , Cromatografia Líquida/métodos , Solventes/químicaRESUMO
We have realized a comb system with a 30 GHz mode spacing, 62 % available wavelength coverage in the visible region, and nearly 40 dB spectral contrast by combining a robust erbium-doped-fiber-based femtosecond laser, mode filtering with newly designed optical cavities, and broadband-visible-range comb generation using a chirped periodically-poled LiNbO3 ridge waveguide. Furthermore, it is suggested that this system produces a spectrum with little change over 29 months. These features of our comb will contribute to fields requiring broad-mode-spacing combs, including astronomical observations, such as exoplanet exploration and the verification of the cosmic accelerating expansion.