Cardiac-to-Bronchial Fistula in Hepatocellular Carcinoma: A Case Report.

Hepatocellular carcinoma (HCC) stands as a significant contributor to cancer-related mortality globally. While the acute and often fatal manifestations of locally advanced HCC primarily present within the abdomen, it is crucial to recognize that the respiratory and circulatory systems can also fall victim due to the liver's unique anatomical position within the body. Here, we present the case of a 63-year-old male recently diagnosed with locally advanced HCC with vascular invasion. Shortly after receiving target therapy and focal radiotherapy, the patient developed repeated secondary infections and a persistent diaphragmatic defect. As the necrotic tissue invaded the pleural space, subsequent tumor-to-bronchial and tumor-to-cardiac fistulas emerged, resulting in an abnormal connection between the respiratory and cardiovascular systems, leading to massive air emboli in circulation. This report highlights the risk of supradiaphragmatic complications in HCC patients with post-treatment secondary infections, particularly in patients predisposed to developing diaphragmatic defects.

Bidirectional associations between hyperopia, myopia, astigmatism, and strabismus, and attention-deficit/hyperactivity disorder in children: a national population-based cohort study

Objectives: The present study analyzed the reciprocal relationships between four common pediatric ophthalmic diseases (i.e., hyperopia, myopia, astigmatism, and strabismus) and attention‐deficit/hyperactivity disorder (ADHD) in children. Methods: This study enrolled 86,028 children with ADHD and 1,798,673 children without ADHD in the Taiwan Maternal and Child Health Database who were born at any time from 2004 to 2017. Cox proportional hazards regression models were used to estimate the bidirectional relationships of the four ophthalmic diseases with ADHD in children after adjusting for age, sex, and gestational age at birth. Survival curves for time-to-event variables were estimated using the Kaplan-Meier method, and the log-rank test was used to compare the curves. Results: The results indicated that ADHD significantly predicted the occurrence of hyperopia, myopia, astigmatism, and strabismus. Furthermore, hyperopia, myopia, astigmatism, and strabismus significantly predicted the occurrence of ADHD. The time between enrollment and ADHD diagnosis was shorter for patients with ophthalmic diseases than for the control group, and the time between enrollment and ophthalmic disease diagnosis was also shorter for ADHD patients than for the control group. Sex differences were found in the associations between ADHD and ophthalmic diseases. Conclusion: Clinicians should monitor children with ADHD for hyperopia, myopia, astigmatism, and strabismus to ensure appropriate treatment, and vice versa.

Bidirectional associations between hyperopia, myopia, astigmatism, and strabismus, and attention-deficit/hyperactivity disorder in children: a national population-based cohort study.

OBJECTIVES: The present study analyzed the reciprocal relationships between four common pediatric ophthalmic diseases (i.e., hyperopia, myopia, astigmatism, and strabismus) and attention-deficit/hyperactivity disorder (ADHD) in children. METHODS: This study enrolled 86,028 children with ADHD and 1,798,673 children without ADHD in the Taiwan Maternal and Child Health Database who were born at any time from 2004 to 2017. Cox proportional hazards regression models were used to estimate the bidirectional relationships of the four ophthalmic diseases with ADHD in children after adjusting for age, sex, and gestational age at birth. Survival curves for time-to-event variables were estimated using the Kaplan-Meier method, and the log-rank test was used to compare the curves. RESULTS: The results indicated that ADHD significantly predicted the occurrence of hyperopia, myopia, astigmatism, and strabismus. Furthermore, hyperopia, myopia, astigmatism, and strabismus significantly predicted the occurrence of ADHD. The time between enrollment and ADHD diagnosis was shorter for patients with ophthalmic diseases than for the control group, and the time between enrollment and ophthalmic disease diagnosis was also shorter for ADHD patients than for the control group. Sex differences were found in the associations between ADHD and ophthalmic diseases. CONCLUSION: Clinicians should monitor children with ADHD for hyperopia, myopia, astigmatism, and strabismus to ensure appropriate treatment, and vice versa.

Efforts to improve the surgical outcome for exotropia and investigation of the insertion locations of the extraocular muscles.

In our previous retrospective study, we found that using the strabismus surgery dosages established by western strabismus mentors tends to result in undercorrection of Taiwanese exotropia (XT) patients compared with those in western populations. We also discovered that the location of extraocular muscle (EOM) insertion could vary by ethnicity. In this study, using a generalized estimation equation model, we compared the XT surgery outcome between augmented and original strabismus surgery dosages in Taiwanese patients. We also conducted an observational study to investigate the horizontal EOM insertion location in a Taiwanese population and compared the data with Dr. Apt L.'s study. For Taiwanese XT patients, augmented surgical dosages resulted in significantly better outcome at 6 months and 1 year postoperatively compared with original surgical dosages (p = 0.003 and p < 0.001, respectively). The distance from the lateral recuts muscle (LR) insertion location to the limbus was significantly shorter in Taiwanese than in white Americans (6.5 vs. 6.9 mm, respectively, p = 0.0001). Furthermore, the medial rectus muscle and LR insertion locations differed significantly between males and females (p < 0.001 and p = 0.023, respectively). The patients' sex did not affect the surgery outcome. Augmented surgery doses modified from western strabismus mentors produce better surgery outcome for Taiwanese XT patients. Surgeons may require country-specific guidelines for strabismus surgery dosage. We also demonstrated a simple method for young ophthalmologists to establish their own normograms to improve their surgical success rate. Our study confirms that LR insertion locations differ between Taiwanese and White Americans.

Nordalbergin Exerts Anti-Neuroinflammatory Effects by Attenuating MAPK Signaling Pathway, NLRP3 Inflammasome Activation and ROS Production in LPS-Stimulated BV2 Microglia.

Microglia-associated neuroinflammation is recognized as a critical factor in the pathogenesis of neurodegenerative diseases; however, there is no effective treatment for the blockage of neurodegenerative disease progression. In this study, the effect of nordalbergin, a coumarin isolated from the wood bark of Dalbergia sissoo, on lipopolysaccharide (LPS)-induced inflammatory responses was investigated using murine microglial BV2 cells. Cell viability was assessed using the MTT assay, whereas nitric oxide (NO) production was analyzed using the Griess reagent. Secretion of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) was detected by the ELISA. The expression of inducible NO synthase (iNOS), cyclooxygenase (COX)-2, mitogen-activated protein kinases (MAPKs) and NLRP3 inflammasome-related proteins was assessed by Western blot. The production of mitochondrial reactive oxygen species (ROS) and intracellular ROS was detected using flow cytometry. Our experimental results indicated that nordalbergin ≤20 µM suppressed NO, IL-6, TNF-α and IL-1ß production; decreased iNOS and COX-2 expression; inhibited MAPKs activation; attenuated NLRP3 inflammasome activation; and reduced both intracellular and mitochondrial ROS production by LPS-stimulated BV2 cells in a dose-dependent manner. These results demonstrate that nordalbergin exhibits anti-inflammatory and anti-oxidative activities through inhibiting MAPK signaling pathway, NLRP3 inflammasome activation and ROS production, suggesting that nordalbergin might have the potential to inhibit neurodegenerative disease progression.

Magnolol regulates miR-200c-3p to inhibit epithelial-mesenchymal transition and retinoblastoma progression by modulating the ZEB1/E-cadherin axis in vitro and in vivo.

BACKGROUND: Retinoblastoma, the most common pediatric intraocular malignancy, can develop during embryogenesis, with most children being diagnosed at 3-4 years of age. Multimodal therapies are typically associated with high levels of cytotoxicity and side effects. Therefore, the development of novel treatments with minimal side effects is crucial. Magnolol has a significant anti-tumor effect on various cancers. However, its antitumor effect on retinoblastoma remains unclear. PURPOSE: The study aimed to determine the effects of magnolol on the regulation of EMT, migration, invasion, and cancer progression in retinoblastoma and the modulation of miR-200c-3p expression and the Wnt/ zinc finger E-box binding homeobox 1 (ZEB1)/E-cadherin axis in vivo and in vitro. METHODS: The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay was used to evaluate magnolol-induced cell toxicity in the Y79 retinoblastoma cell line. Flow cytometry and immunostaining assays were performed to investigate the magnolol-regulated mitochondrial membrane potential and the intracellular and mitochondrial reactive oxygen species levels in Y79 retinoblastoma cells. Orthotopic and subcutaneous xenograft experiments were performed in eight-week-old male null mice to study retinoblastoma progression and metastasis. In situ hybridization and quantitative reverse transcription polymerase chain reaction (RT-qPCR) assays were performed to evaluate the level of the anti-cancer miRNA miR-200c-3p. The mRNA and protein levels of E-cadherin, ß-catenin, α-smooth muscle actin (α-SMA), fibronectin-1, and ZEB1 were analyzed using RT-qPCR, immunoblot, immunocytochemistry, and immunohistochemistry assays in vitro and in vivo. RESULTS: Magnolol increased E-cadherin levels and reduced the activation of the EMT signaling pathway, EMT, tumor growth, metastasis, and cancer progression in the Y79 retinoblastoma cell line as well as in the orthotopic and subcutaneous xenograft animal models. Furthermore, magnolol increased the expression of miR-200c-3p. Our results demonstrate that miRNA-200c-3p inhibits EMT progression through the Wnt16/ß-catenin/ZEB1/E-cadherin axis, and the ZEB1 silencing response shows that miR-200c-3p regulates ZEB1-mediated EMT in retinoblastoma. CONCLUSION: Magnolol has an antitumor effect by increasing E-cadherin and miRNA-200c-3p expression to regulate ZEB1-mediated EMT and cancer progression in retinoblastoma. The anti-tumor effect of magnolol by increasing E-cadherin and miRNA-200c-3p expression to regulate ZEB1-mediated EMT and cancer progression in retinoblastoma has been elucidated for the first time.

A comparative multicentric long-term study of un-augmented modified Nishida procedure vs augmentation in unilateral sixth nerve palsy.

PURPOSE: To compare the effectiveness of three procedures: modified Nishida procedure alone vs modified Nishida procedure combined with medial rectus recession (MRc) vs modified Nishida procedure combined with MRc and botulinum toxin (BT) for severe unilateral sixth nerve palsy. DESIGN: Consecutive, interventional case series. METHODS: The medical records of a consecutive series of patients with severe unilateral sixth nerve palsy who underwent modified Nishida procedure in multiple centres were reviewed. Surgical technique was decided preoperatively at the surgeon's discretion. The preoperative and postoperative findings were compared. RESULTS: Of the 43 patients with abducens palsy that received the procedure, 32 were included (mean age 38.6 ± 19.8 years). Mean preoperative deviation was 63.0 ± 27.3 prism dioptres (PD) and mean limitation of abduction -4.5 ± 1.2. Five patients underwent a modified Nishida procedure alone, 24 patients had an additional MRc and 3 patients were also injected with BT. Overall, the average correction of modified Nishida technique by itself was 29.4 ± 6.6 PD (range 20-36) and adding a MRc corrected 62.6 ± 23.8 PD (range 24-120). Modified Nishida procedure, MRc and BT altogether corrected 95.0 ± 18.0 PD (range 75-110). No postoperative complications were observed in any of the patients. CONCLUSIONS: Excellent outcomes with fewer complications are obtained with modified Nishida procedure alone. The need for additional procedures such as MRc and BT which increase the effect in primary position can be determined depending on passive duction and preoperative horizontal deviation.

Punicalagin Attenuates LPS-Induced Inflammation and ROS Production in Microglia by Inhibiting the MAPK/NF-κB Signaling Pathway and NLRP3 Inflammasome Activation.

Purpose: Neurodegenerative diseases are associated with neuroinflammation along with activation of microglia and oxidative stress, but currently lack effective treatments. Punicalagin is a natural bio-sourced product that exhibits anti-inflammatory effects on several chronic diseases; however, the anti-inflammatory and anti-oxidative effects on microglia have not been well examined. This study aimed to investigate the effects of punicalagin on LPS-induced inflammatory responses, NLRP3 inflammasome activation, and the production of ROS using murine microglia BV2 cells. Methods: BV2 cells were pre-treated with punicalagin following LPS treatment to induce inflammation. The secretion of NO and PGE2 was analyzed by Griess reagent and ELISA respectively, while the expressions of iNOS, COX-2, STAT3, ERK, JNK, and p38 were analyzed using Western blotting, the production of IL-6 was measured by ELISA, and the activity of NF-κB was detected using promoter reporter assay. To examine whether punicalagin affects NLRP3 inflammasome activation, BV2 cells were stimulated with LPS and then treated with ATP or nigericin. The secretion of IL-1ß was measured by ELISA. The expressions of NLRP3 inflammasome-related proteins and phospho IκBα/IκBα were analyzed using Western blotting. The production of intracellular and mitochondrial ROS was analyzed by flow cytometry. Results: Our results showed that punicalagin attenuated inflammation with reduction of pro-inflammatory mediators and cytokines including iNOS, COX-2, IL-1ß, and reduction of IL-6 led to inhibition of STAT3 phosphorylation by LPS-induced BV2 cells. Punicalagin also suppressed the ERK, JNK, and p38 phosphorylation, attenuated NF-κB activity, inhibited the activation of the NLRP3 inflammasome, and reduced the production of intracellular and mitochondrial ROS by LPS-induced BV2 cells. Conclusion: Our results demonstrated that punicalagin attenuated LPS-induced inflammation through suppressing the expression of iNOS and COX-2, inhibited the activation of MAPK/NF-κB signaling pathway and NLRP3 inflammasome, and reduced the production of ROS in microglia, suggesting that punicalagin might have the potential in treating neurodegenerative diseases.

Mycotoxin Zearalenone Attenuates Innate Immune Responses and Suppresses NLRP3 Inflammasome Activation in LPS-Activated Macrophages.

Zearalenone (ZEA) is a mycotoxin that has several adverse effects on most mammalian species. However, the effects of ZEA on macrophage-mediated innate immunity during infection have not been examined. In the present study, bacterial lipopolysaccharides (LPS) were used to induce the activation of macrophages and evaluate the effects of ZEA on the inflammatory responses and inflammation-associated signaling pathways. The experimental results indicated that ZEA suppressed LPS-activated inflammatory responses by macrophages including attenuating the production of proinflammatory mediators (nitric oxide (NO) and prostaglandin E2 (PGE2)), decreased the secretion of proinflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and IL-6), inhibited the activation of c-Jun amino-terminal kinase (JNK), p38 and nuclear factor-κB (NF-κB) signaling pathways, and repressed the nucleotide-binding and oligomerization domain (NOD)-, leucine-rich repeat (LRR)- and pyrin domain-containing protein 3 (NLRP3) inflammasome activation. These results indicated that mycotoxin ZEA attenuates macrophage-mediated innate immunity upon LPS stimulation, suggesting that the intake of mycotoxin ZEA-contaminated food might result in decreasing innate immunity, which has a higher risk of adverse effects during infection.

Toxicity of amantadine hydrochloride on cultured bovine cornea endothelial cells.

Amantadine hydrochloride (HCl) is commonly prescribed for treating influenza A virus infection and Parkinson's disease. Recently, several studies have indicated that the use of amantadine HCl is associated with corneal edema; however, the cytotoxic effect of amantadine HCl has not been investigated. In the present study, the effects of amantadine HCl on cell growth, proliferation, and apoptosis in bovine cornea endothelial cells, and in vitro endothelial permeability were examined. Results showed that lower doses of amantadine HCl do not affect cell growth (≤ 20 µΜ), whereas higher doses of amantadine HCl inhibits cell growth (≥ 50 µΜ), induces apoptosis (2000 µΜ), increases sub-G1 phase growth arrest (2000 µΜ), causes DNA damage (≥ 1000 µΜ), and induces endothelial hyperpermeability (≥ 1000 µΜ) in bovine cornea endothelial cells; additionally, we also found that amantadine HCl attenuates the proliferation (≥ 200 µΜ) and arrests cell cycle at G1 phase (≥ 200 µΜ) in bovine cornea endothelial cells. In the present study, we measured the cytotoxic doses of amantadine HCl on cornea endothelial cells, which might be applied in evaluating the association of corneal edema.

A reassessment and comparison of the Landolt C and tumbling E charts in managing amblyopia.

Current criteria for amblyopia do not account for difference in visual acuity charts. This prospective observational study analyzed 100 children younger than 10 years treated at a tertiary referral center. Visual acuity was separately tested in each eye using Landolt C and tumbling E charts in a random order. For each chart, receiver operating characteristic curve analysis was performed to determine the best cutoff for visual acuity score. Main outcome measures included the difference in visual acuity scores between the two charts, the feasibility of repeated testing of visual acuity in each eye, and amblyopia cutoff values for each chart. Mean logMAR visual acuity scores obtained by tumbling E chart were significantly better than those obtained by Landolt C chart. For amblyopia, the best cutoff values were < + 0.14 (20/27 Snellen equivalent) for tumbling E chart and < + 0.24 (20/35 Snellen equivalent) for Landolt C chart. For children under 10 years old, visual acuity scores for tumbling E chart were significantly better than those for Landolt C chart. We suggest that amblyopia management in children should account for age and the type of visual acuity chart used.

Thrombospondin 1-induced exosomal proteins attenuate hypoxia-induced paraptosis in corneal epithelial cells and promote wound healing.

Thrombospondin-1 (TSP1) is involved in corneal wound healing caused by chemical injury. Herein, we examined the effects of TSP1 on hypoxia-induced damages and wound-healing activity in human corneal epithelial (HCE) cells. Exosomal protein expression was determined using liquid chromatography-tandem mass spectrometry, and HCE cell migration and motility were examined through wound-healing assay and time-lapse microscopy. Reestablishment of cell junctions by TSP1 was assessed through confocal microscopy and 3D image reconstruction. Our results show that CoCl2 -induced hypoxia promoted HCE cell death by paraptosis. TSP1 protected these cells against paraptosis by attenuating mitochondrial membrane potential depletion, swelling and dilation of endoplasmic reticulum and mitochondria, and mitochondrial fission. Exosomes isolated from HCE cells treated with TSP1 contained wound healing-associated proteins that were taken up by HCE cells to promote tissue remodeling and repair. TSP1 protected HCE cells against hypoxia-induced damages and inhibited paraptosis progression by promoting cell migration, cell-cell adhesion, and extracellular matrix remodeling. These findings indicate that TSP1 ameliorates hypoxia-induced paraptosis in HCE cells and promotes wound healing and remodeling by regulating exosomal protein expression. TSP1 may, therefore, play important roles in the treatment of hypoxia-associated corneal diseases.

Effectiveness of Multidisciplinary Care for Chronic Kidney Disease: A Systematic Review.

BACKGROUND: Chronic kidney disease (CKD) is a common chronic disease. As this disease is extremely complex, multidisciplinary care (MDC) is needed to provide complete and continuous care. AIM: A systematic literature review was performed to examine the constituents of MDC, the content of MDC interventions, and the health outcomes in CKD patients receiving MDC. METHODS: Searches of five Chinese and English databases for studies of CKD patients who had received MDC from 2007 to 2019 revealed 11 studies, which comprised 16,066 CKD patients. The Physiotherapy Evidence Database scale (Physiotherapy Evidence Database, 2017) was used to appraise study quality for randomized controlled trials, and the Joanna Briggs Institute Critical Appraisal tools (Joanna Briggs Institute, 2017) were for cohort studies. RESULTS: The MDC teams that provided comprehensive medical care for these patients included nephrologists, nurses, surgeons, general practitioners, pharmacists, psychotherapists, social workers, nutritionists, and other specialists. The literature review revealed that MDC for CKD slows the decline in estimated glomerular filtration rate and decreases patient mortality, the risk of renal replacement therapy, the need for emergent dialysis, and annual medical costs. Analyses of biochemical markers in the CKD patients showed that MDC improves control of serum levels of calcium and phosphate, improves control of parathyroid hormone, and reduces proteinuria and fasting blood glucose values. However, further studies are needed to determine the effects of MDC on all-cause mortality, blood pressure control, hospitalization rate, hospitalization for cardiovascular or infection events, medications use, and other biochemical markers in CKD patients. LINKING EVIDENCE TO ACTION: Cross-disciplinary collaboration of healthcare professionals is needed to ensure that patients undergo regular follow-up and periodic assessment of clinical status, in addition to ensuring that relevant resources and assistance are provided in a timely manner. A follow-up period of at least 2 years is also needed to ensure sufficient time to observe MDC results.

Petermann-factor sensitivity limit near an exceptional point in a Brillouin ring laser gyroscope.

Exceptional points are singularities of open systems, and among their many remarkable properties, they provide a way to enhance the responsivity of sensors. Here we show that the improved responsivity of a laser gyroscope caused by operation near an exceptional point is precisely compensated by increasing laser noise. The noise, of fundamental origin, is enhanced because the laser mode spectrum loses the oft-assumed property of orthogonality. This occurs as system eigenvectors coalesce near the exceptional point and a bi-orthogonal analysis confirms experimental observations. While the results do not preclude other possible advantages of the exceptional-point-enhanced responsivity, they do show that the fundamental sensitivity limit of the gyroscope is not improved through this form of operation. Besides being important to the physics of microcavities and non-Hermitian photonics, these results help clarify fundamental sensitivity limits in a specific class of exceptional-point sensor.

Observation of the exceptional-point-enhanced Sagnac effect.

Exceptional points (EPs) are special spectral degeneracies of non-Hermitian Hamiltonians that govern the dynamics of open systems. At an EP, two or more eigenvalues, and the corresponding eigenstates, coalesce1-3. Recently, it was predicted that operation of an optical gyroscope near an EP results in improved response to rotations4,5. However, the performance of such a system has not been examined experimentally. Here we introduce a precisely controllable physical system for the study of non-Hermitian physics and nonlinear optics in high-quality-factor microresonators. Because this system dissipatively couples counter-propagating lightwaves within the resonator, it also functions as a sensitive gyroscope for the measurement of rotations. We use our system to investigate the predicted EP-enhanced Sagnac effect4,5 and observe a four-fold increase in the Sagnac scale factor by directly measuring rotations applied to the resonator. The level of enhancement can be controlled by adjusting the system bias relative to the EP, and modelling results confirm the observed enhancement. Moreover, we characterize the sensitivity of the gyroscope near the EP. Besides verifying EP physics, this work is important for the understanding of optical gyroscopes.

Searching for Exoplanets Using a Microresonator Astrocomb.

Orbiting planets induce a weak radial velocity (RV) shift in the host star that provides a powerful method of planet detection. Importantly, the RV technique provides information about the exoplanet mass, which is unavailable with the complementary technique of transit photometry. However, RV detection of an Earth-like planet in the 'habitable zone'1 requires extreme spectroscopic precision that is only possible using a laser frequency comb (LFC)2. Conventional LFCs require complex filtering steps to be compatible with astronomical spectrographs, but a new chip-based microresonator device, the Kerr soliton microcomb3-8, is an ideal match for astronomical spectrograph resolution and can eliminate these filtering steps. Here, we demonstrate an atomic/molecular line-referenced soliton microcomb as a first in-the-field demonstration of microcombs for calibration of astronomical spectrographs. These devices can ultimately provide LFC systems that would occupy only a few cubic centimetres9,10, thereby greatly expanding implementation of these technologies into remote and mobile environments beyond the research lab.

The characteristics of premature infants with transient corneal haze.

BACKGROUND: The etiology of transient corneal haze in premature infants is not known and how it relates to clinical outcomes in premature infants is not clear. OBJECTIVES: To study associated factors of transient corneal haze in premature infants. METHODS: We performed a retrospective study of 261 premature infants from retinopathy of prematurity (ROP) screening in the neonatal intensive care unit at a tertiary referral hospital. Characteristics of premature infants with and without corneal haze were analyzed by correlation tests, Chi-square tests, and logistic regressions were used for statistical analyses. Associations between corneal haze and birth weight (BW), gestational age at birth (GA), central corneal thickness, intraocular pressure, and other systemic and ophthalmic data were evaluated. RESULTS: The incidence of corneal haze was 13.4%. Lower BW, lower GA, packed red blood cells (RBC) transfusion, more days on oxygen, older maternal age, bronchopulmonary disease, and stage 3 ROP are associated with corneal haze. The severity of corneal haze decreased with infants' postmenstrual age. Multivariate logistic regression analyses revealed that BW and maternal age are the most important predictors of corneal haze. CONCLUSION: Low BW and older maternal age are the most important predictors of corneal haze in premature infants. Premature infants with corneal haze could carry more systemic and ocular morbidities. Hence they may require more clinical attention. Corneal haze is unlikely to hinder the treatment of ROP. However, it is possible that corneal haze could hinder the examination of ROP in some infants. If corneal haze does interfere with ROP screening, a closer, more conservative follow-up schedule with a senior ophthalmologist experienced in managing ROP is recommended.

Towards visible soliton microcomb generation.

Frequency combs have applications that extend from the ultra-violet into the mid-infrared bands. Microcombs, a miniature and often semiconductor-chip-based device, can potentially access most of these applications, but are currently more limited in spectral reach. Here, we demonstrate mode-locked silica microcombs with emission near the edge of the visible spectrum. By using both geometrical and mode-hybridization dispersion control, devices are engineered for soliton generation while also maintaining optical Q factors as high as 80 million. Electronics-bandwidth-compatible (20 GHz) soliton mode locking is achieved with low pumping powers (parametric oscillation threshold powers as low as 5.4 mW). These are the shortest wavelength soliton microcombs demonstrated to date and could be used in miniature optical clocks. The results should also extend to visible and potentially ultra-violet bands.