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Arshad M Khanani,1,2 Matthew W Russell,3,4 Aamir A Aziz,1,2 Carl J Danzig,5,6 Christina Y Weng,7 David A Eichenbaum,8,9 Rishi P Singh3,4 1Sierra Eye Associates, Reno, NV, USA; 2The University of Nevada, Reno School of Medicine, Reno, NV, USA; 3Center for Ophthalmic Bioinformatics, Cole Eye Institute, Cleveland Clinic, Cleveland, OH, USA; 4Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH, USA; 5Rand Eye Institute, Deerfield, FLA, USA; 6Florida Atlantic University, Charles E. Schmidt College of Medicine, Boca Raton, FL, USA; 7Baylor College of Medicine, Houston, TX, USA; 8Retina Vitreous Associates of Florida, St Petersburg, FLA, USA; 9University of South Florida Morsani College of Medicine, Tampa, FLA, USACorrespondence: Arshad M Khanani 950 Ryland Street, Reno, NV, 89502, USATel +775 329-0286Fax +775-329-0849Email arshad.khanani@gmail.comAbstract: The Ang/Tie2 pathway complements VEGF-mediated activity in retinal vascular diseases such as DME, AMD, and RVO by decreasing vascular integrity, increasing neovascularization, and increasing inflammatory signaling. Faricimab is a bispecific antibody that has been developed as an inhibitor of both VEGF and Ang2 that has shown positive results in phase I, II and III trials. Recent Year 1 data from phase III clinical trials YOSEMITE, RHINE, TENAYA, and LUCERNE have confirmed the efficacy, safety, durability, and superiority of faricimab in patients with DME and nAMD. Faricimab, if approved, may significantly decrease treatment burden in patients with retinal vascular diseases to a greater extent than would current standard of care anti-VEGF injections.Keywords: Ang/Tie, faricimab, YOSEMITE, RHINE, TENAYA, LUCERNE

Jie Gao,1 Rehan M Hussain,2 Christina Y Weng1 1Department of Ophthalmology, Baylor College of Medicine, Houston, TX, USA; 2Retina Associates, Elmhurst, IL, USACorrespondence: Christina Y WengBaylor College of Medicine, Alkek Eye Center, 1977 Butler Blvd, Houston, TX 77030, USAEmail christina.weng@bcm.eduAbstract: Subretinal gene therapy trials began with the discovery of RPE65 variants and their association with Leber congenital amaurosis. The RPE65 protein is critical for the normal functioning of the visual phototransduction cascade. RPE65 gene knockout animal models were developed and showed similar diseased phenotypes to their human counterparts. Proof of concept studies were carried out in these animal models using subretinal RPE65 gene replacement therapy, resulting in improvements in various visual function markers including electroretinograms, pupillary light responses, and object avoidance behaviors. Positive results in animal models led to Phase 1 human studies using adeno-associated viral vectors. Results in these initial human studies also showed positive impact on visual function and acceptable safety. A landmark Phase 3 study was then conducted by Spark Therapeutics using a dose of 1.5 x1011 vector genomes after dose-escalation studies confirmed its efficacy and safety. Multi-luminance mobility testing was used to measure the primary efficacy endpoint due to its excellent reliability in detecting the progression of inherited retinal diseases. After the study met its primary endpoint, the Food and Drug Administration approved voretigene neparvovec (Luxturna®) for use in RPE65-associated inherited retinal diseases.Keywords: gene therapy, inherited retinal diseases, Leber congenital amaurosis, Luxturna, RPE65, voretigene neparvovec, retinitis pigmentosa, retina

Asad Loya,1 Talha Ayaz,2 Christina Y Weng3 1School of Medicine, Baylor College of Medicine, Houston, TX, USA; 2School of Medicine, University of Texas Medical Branch at Galveston, Galveston, TX, USA; 3Department of Ophthalmology,Cullen Eye Institute, Baylor College of Medicine, Houston, TX, USACorrespondence: Christina Y WengDepartment of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, TX, USATel +1 713 798-6100Email christina.weng@bcm.eduBackground: An ocular or periocular malignancy can profoundly impact patients’ lives as they cope with the challenges of a potentially life-threatening diagnosis and the exhaustive treatment process it entails. An amalgam of biopsychosocial factors can influence prognosis. This study aims to determine whether marital status impacts the long-term survival of patients with these malignancies.Methods: A retrospective analysis of the Surveillance, Epidemiology, and End Results (SEER) database was performed. Patients with ocular and periocular malignancies diagnosed between 1973 and 2015 were included. The association between survival and marital status was assessed using univariate and multivariate Cox regression. Adjusted covariates included demographic, tumor, and treatment data.Results: A total of 3159 patients with a mean±SD follow-up period of 6.47± 4.62 (range 0– 17.9) years were studied. At the time of diagnosis, 63.4% (2004/3159) of the cohort were married, 12.9% (409/3159) were single, 16.3% (514/3159) were widowed, and 7.3% (232/3159) were divorced. The mean±SD age of the cohort was 64.4± 15.17 (range 26– 100) years, with histology distributed as 14.6% (462/3159) melanoma, 84.5% (2669/3159) lymphoma, and 0.9% (28/3159) plasmacytoma. Adjusted all-cause mortality risk was higher in single (HR, 1.885, 95% CI 1.535 to 2.314; P< 0.001), widowed (HR, 1.382, 95% CI 1.169 to 1.635; P< 0.001), and divorced (HR, 1.637, 95% CI 1.271 to 2.109; P< 0.001) individuals compared to married individuals. Similarly, adjusted cause-specific mortality risk was higher in single (HR, 1.835, 95% CI 1.332 to 2.528; P< 0.001), widowed (HR, 1.376, 95% CI 1.025 to 1.847; P=0.033), and divorced (HR, 1.873, 95% CI 1.272 to 2.758; P=0.001) individuals compared to married individuals.Conclusion: Unmarried (single, widowed, and divorced) individuals with ocular or periocular malignancies have unmet social support needs resulting in poorer long-term outcomes. Understanding the prognostic role of such psychosocial factors is necessary to improve the identification of and care for patients with inadequate support.Keywords: oncology, ocular, cancer, SEER, relationship, database

Weijie V Lin,1,* Megan N Scott,2,3,* Chosang Tendhar,4 Shazia F Ali,2,3 Zaina Al-Mohtaseb,2,3 Rizwan Shaikh,2,3 Christina Y Weng2,3 1School of Medicine, Baylor College of Medicine, Houston, TX, USA; 2Department of Ophthalmology, Baylor College of Medicine, Houston, TX, USA; 3Ben Taub General Hospital, Harris Health System, Houston, TX, USA; 4Office of Research, Assessment and Planning, Adelphi University, New York, NY, USA*These authors contributed equally to this workCorrespondence: Christina Y WengDepartment of Ophthalmology, Baylor College of Medicine, MBA Alkek Eye Center 1977 Butler Blvd., 3rd Floor, Houston, Texas 77030, USATel +1 713 798-6100Email christina.weng@bcm.eduObjective: To analyze outcomes and complications related to cataract surgery complicated by retained lens fragment (RLF) requiring pars plana vitrectomy (PPV) in a county hospital where procedures are performed by trainees.Methods: Retrospective study of consecutive patients who met inclusion criteria and underwent PPV for RLF in the vitreous cavity at an urban teaching hospital between January 2010 and January 2016 (N=20).Main Outcomes/Measures: Visual acuity was recorded pre- and post-operatively over a follow-up period of 3 to 12 months. Complications and patient factors contributing to outcomes were assessed using paired and unpaired t-tests and multiple linear regression.Results: The average rate of cataract surgery with RLF requiring PPV was 0.75%. Twenty patients met inclusion criteria. Mean pre-operative visual acuity (VA) was logMAR 1.7 (Snellen 20/1000). Nearly half (8/20) had nuclear cataracts grade 3+ or higher. The majority (14/20) had factors predisposing them to cataract surgery complications. Most patients underwent PPV within 1 week (median 6.5 days). At 12-month follow-up, significant (p=0.001) visual acuity (VA) improvement from initial VA was observed, with final mean logMAR 0.6 (± 0.75; Snellen 20/80) and median logMAR 0.35 (Snellen 20/45). Nearly half of the patients had a final Snellen VA ≥ 20/40. Factors associated with less VA improvement were older age and greater proportion of lens dropped (p< 0.01). Complications following PPV included hypotony (5 patients), corneal edema (4), elevated intraocular pressure (IOP) (3), and cystoid macular edema (3).Conclusions/Relevance: Despite patients with advanced pathology and trainee surgeons, rates of cataract surgery-associated RLF requiring PPV at a large tertiary care teaching hospital are similar to reported rates in the literature.Keywords: trainee, complicated cataract surgery, retained lens fragments, resident, fellow, pars plana lensectomy, pars plana vitrectomy, teaching, surgical education

Secretogranin III (Scg3) is a diabetic retinopathy (DR)-restricted angiogenic factor identified in preclinical studies as a target for DR therapy. Previously, our group generated and characterized ML49.3, an anti-Scg3 monoclonal antibody (mAb) which we then converted into an EBP2 humanized antibody Fab fragment (hFab) with potential for clinical application. We also generated anti-Scg3 mT4 mAb and related EBP3 hFab. In this study, to identify the preferred hFab for DR therapy, we compared all four antibodies for binding, neutralizing and therapeutic activities in vitro and in vivo. Octet binding kinetics analyses revealed that ML49.3 mAb, EBP2 hFab, mT4 mAb and EBP3 hFab have Scg3-binding affinities of 35, 8.7, 0.859 and 0.116 nM, respectively. Both anti-Scg3 EBP2 and EBP3 hFabs significantly inhibited Scg3-induced proliferation and migration of human umbilical vein endothelial cells in vitro, and alleviated DR vascular leakage and choroidal neovascularization with high efficacy. Paired assays in DR mice revealed that intravitreally injected EBP3 hFab is 26.4% and 10.3% more effective than EBP2 hFab and aflibercept, respectively, for ameliorating DR leakage. In conclusion, this study confirms the markedly improved binding affinities of hFabs compared to mAbs and further identifies EBP3 hFab as the preferred antibody to develop for anti-Scg3 therapy.

Purpose: To review the evidence on the effectiveness and complications of periocular and intraocular corticosteroid therapies for noninfectious uveitic macular edema., Methods: A literature search of the PubMed database was conducted last in December 2021 and a post-assessment search was conducted in March 2023. The searches were limited to articles published in English and no date restrictions were imposed. The combined searches yielded 739 citations; 53 articles were selected for inclusion because the studies (1) evaluated periocular corticosteroid injection, intraocular corticosteroid injection or implant, suprachoroidal corticosteroid injection, or a combination thereof for uveitic macular edema; (2) had outcomes that included visual acuity (VA) or macular edema assessed clinically or imaged by OCT or fluorescein angiography; and (3) included more than 20 patients., Results: This assessment reviewed 23 articles that provided level I or level II evidence from 18 studies on the use of periocular, suprachoroidal, and intravitreal triamcinolone acetonide injections and intravitreal dexamethasone and fluocinolone acetonide implants or inserts in noninfectious uveitic macular edema. These reports consistently demonstrated that all investigated periocular and intraocular corticosteroid therapies improved VA, macular structure, or both. One comparative study showed that intravitreal triamcinolone acetonide injection and the dexamethasone intravitreal implant had effectiveness superior to that of periocular triamcinolone acetonide injection for these outcomes. As a group, the studies highlighted the potential for these therapies to elevate intraocular pressure and to accelerate cataract formation., Conclusions: The published literature provides high-quality evidence that periocular and intraocular corticosteroid therapies are effective and safe for the treatment of noninfectious uveitic macular edema. However, information on the relative effectiveness and complication rates across the different therapies is limited., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background and Objective: Correlations between the image analysis of CT scan, lung function and quality of life in patients with idiopathic pulmonary fibrosis (IPF) remain unclear. This study aimed to investigate the impacts of pulmonary blood-vessel distribution and the extent of fibrosis on the lung function and quality of life of patients with IPF., Methods: Patients were enrolled in an IPF registry and had completed pulmonary function tests, chest HRCT, St. George Respiratory Questionnaire (SGRQ) and echocardiography. Pulmonary blood-vessel distribution, specific image-derived airway volume (siVaw) and fibrosis extent (siVfib) were quantitatively calculated by functional respiratory imaging on HRCT., Results: The study subjects were categorized into DLco <40% pred. (n = 40) and DLco ≥40% pred. (n = 19) groups. Patients with DLco <40% pred. had significantly higher scores of SGRQ, composite physiologic index (CPI), exercise oxygen desaturation (∆SpO 2 ), siVaw, lower FVC% pred. and 6-minute walking distance% pred. The proportion of small blood vessels in the upper lobes (BV5PR-UL) was significantly correlated with CPI, DLco % Pred., FVC% pred., SGRQ and ∆SpO 2 . Only BV5PR-UL had a significant impact on all indices but not BV5PR in the lower lobes (BV5PR-LL). siVfib was significantly negatively correlated with BV5PR-UL, DLco% pred. and FVC% pred., as well as positively correlated with CPI, ∆SpO 2 and siVaw., Conclusion: BV5PR-UL and siVfib had significant correlations with lung function and may become important indicators to assess the severity of IPF and the impact on quality of life., (© 2024 The Author(s). Respirology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Respirology.)

Typically, gel-like materials consist of a polymer network structure in a solvent. In this work, a gel-like material is developed in a deep eutectic solvent (DES) without the presence of a polymer network, achieved simply by adding microgels. The DES is composed of choline chloride and citric acid and remains stably in a supercooled state at room temperature, exhibiting Newtonian fluid behavior with high viscosity. When the microgel (Carbopol) concentration exceeds 2 wt %, the DES undergoes a transition from a liquid to a soft gel state, characterized as a granular eutectogel. The soft gel characteristics of eutectogels exhibit a yield stress, and their storage moduli exceed the loss moduli. The yield stress and storage moduli are observed to increase with increasing microgel concentration. In contrast, the ion conductivity decreases with increasing microgel concentration but eventually levels off. Because the eutectogel can dissolve completely in excess water, it is a physical gel-like material, attributed to the densely packed structure of microgels in the supercooled DES. Due to the absence of networks, the granular eutectogel has the capability to self-heal simply by being pushed together after being cut into two pieces.

Purpose: This American Academy of Ophthalmology Ophthalmic Technology Assessment aims to assess the effectiveness of conventional teleretinal screening (TS) in detecting diabetic retinopathy (DR) and diabetic macular edema (DME)., Methods: A literature search of the PubMed database was conducted most recently in July 2023 to identify data published between 2006 and 2023 on any of the following elements related to TS effectiveness: (1) the accuracy of TS in detecting DR or DME compared with traditional ophthalmic screening with dilated fundus examination or 7-standard field Early Treatment Diabetic Retinopathy Study photography, (2) the impact of TS on DR screening compliance rates or other patient behaviors, and (3) cost-effectiveness and patient satisfaction of TS compared with traditional DR screening. Identified studies then were rated based on the Oxford Centre for Evidence-Based Medicine grading system., Results: Eight level I studies, 14 level II studies, and 2 level III studies were identified in total. Although cross-study comparison is challenging because of differences in reference standards and grading methods, TS demonstrated acceptable sensitivity and good specificity in detecting DR; moderate to good agreement between TS and reference-standard DR grading was observed. Performance of TS was not as robust in detecting DME, although the number of studies evaluating DME specifically was limited. Two level I studies, 5 level II studies, and 1 level III study supported that TS had a positive impact on overall DR screening compliance, even increasing it by more than 2-fold in one study. Studies assessing cost-effectiveness and patient satisfaction were not graded formally, but they generally showed that TS was cost-effective and preferred by patients over traditional surveillance., Conclusions: Conventional TS is an effective approach to DR screening not only for its accuracy in detecting referable-level disease, but also for improving screening compliance in a cost-effective manner that may be preferred by patients. Further research is needed to elucidate the ideal approach of TS that may involve integration of artificial intelligence or other imaging technologies in the future., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To review recent technological advancement in imaging, surgical visualization, robotics technology, and the use of artificial intelligence in surgical vitreoretinal (VR) diseases., Background: Technological advancements in imaging enhance both preoperative and intraoperative management of surgical VR diseases. Widefield imaging in fundal photography and OCT can improve assessment of peripheral retinal disorders such as retinal detachments, degeneration, and tumors. OCT angiography provides a rapid and noninvasive imaging of the retinal and choroidal vasculature. Surgical visualization has also improved with intraoperative OCT providing a detailed real-time assessment of retinal layers to guide surgical decisions. Heads-up display and head-mounted display utilize 3-dimensional technology to provide surgeons with enhanced visual guidance and improved ergonomics during surgery. Intraocular robotics technology allows for greater surgical precision and is shown to be useful in retinal vein cannulation and subretinal drug delivery. In addition, deep learning techniques leverage on diverse data including widefield retinal photography and OCT for better predictive accuracy in classification, segmentation, and prognostication of many surgical VR diseases., Conclusion: This review article summarized the latest updates in these areas and highlights the importance of continuous innovation and improvement in technology within the field. These advancements have the potential to reshape management of surgical VR diseases in the very near future and to ultimately improve patient care., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Two-dimensional layered semiconductor materials as a distinctive class of materials are comprehensively explored for widespread applications due to narrow bandgap, controllable morphology, and tunable metal cation composition. Herein, we constructed a sensing platform of surface enhanced Raman spectroscopy (SERS) by combination of nickel‑cobalt layered double hydroxide (NiCo-LDH) microurchins and plasmonic silver nanoparticles (Ag NPs) for fungicide detection of thiabendazole (TBZ). The NiCo-LDHs/Ag-NPs microcomposites consist of NiCo-LDHs microurchins having a large number of nanoneedles deposited with photoreduced Ag NPs. The SERS platform with NiCo-LDHs/Ag-NPs shows an excellent SERS performance for TBZ detection, including an ultra-low detection limit of 1.49 × 10 -11  M, a sublime enhancement factor of 1.71 × 10 9 , high uniformity, good reproducibility, and long-term storage stability. The ultrahigh SERS activity of NiCo-LDH/Ag-NPs can be attributed to strong electromagnetic enhancement in the nanoscale gaps between Ag NPs, massive charge transfer through large-area NiCo-LDH/Ag-NPs interfaces, and the synergistic action of electromagnetic and charge transfer mechanisms. Besides, the unique morphology of NiCo-LDHs/Ag-NPs microcomposite provides a broad surface area for adsorption of TBZ molecules for further Raman signal enhancement. The practicability of the proposed SERS platform is confirmed by detecting TBZ in the real samples of apple juice and river water. The exceptional self-cleaning capability of the NiCo-LDHs/Ag-NPs microcomposite with an retention rate of 81.97 % even after the fifth degradation cycle underscores its impressive sustainable reusability and cost-effectiveness. The findings in this work lay the foundation for the development of high-performance SERS platforms to ensure food safety and environmental protection., Competing Interests: Declaration of competing interest The authors declare no known competing financial interest or personal relationship that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Benzophenones (BPs) are widely used as photoinitiators (PIs) or printing inks in food packaging, which may migrate into foods. However, the toxicity information of some BP analogues, such as 4,4'-bis(diethylamino)-benzophenone (DEAB), 4-phenylbenzophenone (4-PBP), 4 (hydroxymethyl)benzophenone (4-HMBP), those are used as PIs is lacking. Developmental toxicity is a health concern associated with PIs exposure. Recently, alternative non-in vivo methods have been proposed to evaluate the concerned chemicals or better understand the modes of action of certain toxicological endpoints. In this study, using in silico methods, we predicted that BP, DEAB, 4-PBP and 4-HMBP might exhibit developmental toxicity. However, we found that only DEAB is strong embryotoxic and disturbs the early differentiation of mouse embryonic stem cells into three germ layers and cardiomyocytes. DEAB treatment also prevented cardiomyocyte differentiation in human induced pluripotent stem cells (hiPSCs) on day 10. However, BP, 4-PBP and 4-HMBP had no similar effects on cardiomyocyte differentiation on day 10. Transcriptomic analysis revealed that treatment with DEAB significantly decreased the mRNA levels of differentiation-related transcription factors SOX17 and FOXA1, in hiPSCs on day 4. Furthermore, DEAB treatment caused tail malformations and yolk sac edema in zebrafish embryos. To conclude, DEAB may be embryotoxic because it disturbs the early differentiation of stem cells. Further studies are warranted to better understand the health effects of DEAB exposure., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Complications associated with intravitreal anti-VEGF therapies are reported inconsistently in the literature, thus limiting an accurate evaluation and comparison of safety between studies. This study aimed to develop a standardized classification system for anti-VEGF ocular complications using the Delphi consensus process., Design: Systematic review and Delphi consensus process., Participants: Twenty-five international retinal specialists participated in the Delphi consensus survey., Methods: A systematic literature search was conducted to identify complications of intravitreal anti-VEGF agent administration based on randomized controlled trials (RCTs) of anti-VEGF therapy. A comprehensive list of complications was derived from these studies, and this list was subjected to iterative Delphi consensus surveys involving international retinal specialists who voted on inclusion, exclusion, rephrasing, and addition of complications. Furthermore, surveys determined specifiers for the selected complications. This iterative process helped to refine the final classification system., Main Outcome Measures: The proportion of retinal specialists who choose to include or exclude complications associated with anti-VEGF administration., Results: After screening 18 229 articles, 130 complications were categorized from 145 included RCTs. Participant consensus via the Delphi method resulted in the inclusion of 91 complications (70%) after 3 rounds. After incorporating further modifications made based on participant suggestions, such as rewording certain phrases and combining similar terms, 24 redundant complications were removed, leaving a total of 67 complications (52%) in the final list. A total of 14 complications (11%) met exclusion thresholds and were eliminated by participants across both rounds. All other remaining complications not meeting inclusion or exclusion thresholds also were excluded from the final classification system after the Delphi process terminated. In addition, 47 of 75 proposed complication specifiers (63%) were included based on participant agreement., Conclusions: Using the Delphi consensus process, a comprehensive, standardized classification system consisting of 67 ocular complications and 47 unique specifiers was established for intravitreal anti-VEGF agents in clinical trials. The adoption of this system in future trials could improve consistency and quality of adverse event reporting, potentially facilitating more accurate risk-benefit analyses., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to evaluate self-reported functional vision (FV) and the impact of vision loss in patients with USH2A-associated retinal degeneration using a patient-reported outcome (PRO) measure, the Michigan Retinal Degeneration Questionnaire (MRDQ), to correlate MRDQ scores with well-established visual function measurements., Design: An observational cross-sectional study (n = 93) of participants who had Usher Syndrome Type 2 (USH2, n = 55) or autosomal recessive non-syndromic retinitis pigmentosa (ARRP; n = 38) associated with biallelic variants in the USH2A gene., Methods: The study protocol was approved by all ethics boards and informed consent was obtained from each participant. Participants completed the MRDQ at the 48-month study follow-up visit. Disease duration was self-reported by participants. One-way ANOVA was used to compare subgroups (clinical diagnosis, age, disease duration, and full-field stimulus threshold [FST] Blue-Red mediation) on mean scores per domain. Spearman correlation coefficients were used to assess associations between MRDQ domains and visual/retinal function assessments., Results: Of the study sample, 58% were female participants and the median disease duration was 13 years. MRDQ domains were sensitive to differences between subgroups of clinical diagnosis, age, disease duration, and FST Blue-Red mediation. MRDQ domains correlated with static perimetry, microperimetry, full-field stimulus testing, and best-corrected visual acuity (BCVA)., Conclusions: Self-reported FV measured by the MRDQ, when applied to USH2 and ARRP participants, had good distributional characteristics and correlated well with visual function tests. MRDQ adds a new dimension of understanding on vision-related functioning and establishes this PRO tool as an informative measure in evaluating USH2A outcomes.

Background: The cardiac magnetic resonance (CMR) evaluation of right ventricular (RV) morphologic abnormalities in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) is subjective. Here, we aimed to use a quantitative index, the right ventricular scalloping index (RVSI), to standardize the measurement of RV free wall scalloping and aid in the imaging diagnosis., Methods: We retrospectively included 15 patients with definite ARVC and 45 age- and sex-matched patients with idiopathic right ventricular outflow tract ventricular arrhythmia (RVOT-VA) as controls. The RVSI was measured from cine images on four-chamber view to evaluate its ability to distinguish between ARVC and RVOT-VA patients. Other cardiac functional parameters including strain analysis were also performed., Results: The RVSI was significantly higher in the ARVC than RVOT-VA group (1.56 ± 0.23 vs 1.30 ± 0.08, p < 0.001). The diagnostic performance of the RVSI was superior to the RV global longitudinal, circumferential, and radial strains, RV ejection fraction, and RV end-diastolic volume index. The RVSI demonstrated high intraobserver and interobserver reliability (intraclass correlation coefficient, 0.94 and 0.96, respectively). RVSI was a strong discriminator between ARVC and RVOT-VA patients (area under curve [AUC], 0.91; 95% CI, 0.82-0.99). A cutoff value of RVSI ≥1.49 provided an accuracy of 90.0%, specificity of 97.8%, sensitivity of 66.7%, positive predictive value (PPV) of 90.9%, and a negative predictive value (NPV) of 89.8%. In a multivariable analysis, a family history of ARVC or sudden cardiac death (odds ratio, 38.71; 95% CI, 1.48-1011.05; p = 0.028) and an RVSI ≥1.49 (odds ratio, 64.72; 95% CI, 4.58-914.63; p = 0.002) remained predictive of definite ARVC., Conclusion: RVSI is a quantitative method with good performance for the diagnosis of definite ARVC., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2024, the Chinese Medical Association.)

Carbonyl reductases are useful for producing optically active alcohols from their corresponding prochiral ketones. Herein, we applied a computer-assisted strategy to increase the thermostability of a previously constructed carbonyl reductase, LsCR M4 (N101D/A117G/F147L/E145A), which showed an outstanding activity in the synthesis of the ticagrelor precursor (1S)-2-chloro-1-(3,4-difluorophenyl)ethanol. The stability changes introduced by mutations at the flexible sites were predicted using the computational tools FoldX, I-Mutant 3.0, and DeepDDG, which demonstrated that 12 virtually screened mutants could be thermally stable; 11 of these mutants exhibited increased thermostability. Then a superior mutant LsCR M4 -V99L/D150F was screened out from the library that was constructed by iteratively combining the beneficial sites, which showed a 78% increase in activity and a 17.4°C increase in melting temperature compared to LsCR M4 . Our computer-assisted design and combinatorial strategy dramatically increased the efficiency of thermostable enzyme production., (© 2024 Wiley Periodicals LLC.)

A challenge in accurately identifying and classifying left ventricular hypertrophy (LVH) is distinguishing it from hypertrophic cardiomyopathy (HCM) and Fabry disease. The reliance on imaging techniques often requires the expertise of multiple specialists, including cardiologists, radiologists, and geneticists. This variability in the interpretation and classification of LVH leads to inconsistent diagnoses. LVH, HCM, and Fabry cardiomyopathy can be differentiated using T1 mapping on cardiac magnetic resonance imaging (MRI). However, differentiation between HCM and Fabry cardiomyopathy using echocardiography or MRI cine images is challenging for cardiologists. Our proposed system named the MRI short-axis view left ventricular hypertrophy classifier (MSLVHC) is a high-accuracy standardized imaging classification model developed using AI and trained on MRI short-axis (SAX) view cine images to distinguish between HCM and Fabry disease. The model achieved impressive performance, with an F 1-score of 0.846, an accuracy of 0.909, and an AUC of 0.914 when tested on the Taipei Veterans General Hospital (TVGH) dataset. Additionally, a single-blinding study and external testing using data from the Taichung Veterans General Hospital (TCVGH) demonstrated the reliability and effectiveness of the model, achieving an F 1-score of 0.727, an accuracy of 0.806, and an AUC of 0.918, demonstrating the model's reliability and usefulness. This AI model holds promise as a valuable tool for assisting specialists in diagnosing LVH diseases., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Wei-Wen Chen et al.)

Purpose: To describe functional vision (FV) and investigate the relationship between FV, visual acuity (VA), and hill of vision (V TOT ) at baseline in patients with biallelic USH2A variants., Design: Multicenter, international, cross-sectional study., Methods: In individuals with biallelic disease-causing variants in USH2A, clinical diagnosis of Usher syndrome type 2 (USH2) or autosomal recessive nonsyndromic retinitis pigmentosa (ARRP) was based on history of hearing loss and audiology examinations. The VALVVFQ-48 was administered verbally to participants ≥18 years old. VA was measured in both eyes; V TOT was determined from static perimetry in the study eye (better VA). FV scores were calculated using Rasch analysis., Results: Median age of 121 participants (76 with USH2, 45 with ARRP) was 41 years (range: 19-80); 54% were female. FV scores varied from -2.0 to 7.6 logits (median [interquartile range (IQR)]: 2.8 [1.5-3.8]). ARRP and USH2 participants had similar FV scores, both before [mean (95% CI): 2.8 (2.3-3.4) and 2.7 (2.3-3.2), respectively], and after [mean (95% CI): 2.5 (2.1-3.0) and 2.9 (2.6-3.3), respectively; P = .24] adjusting for age, VA, disease duration, and V TOT . VA and V TOT accounted for 29% and 26% of the variance in FV scores, respectively (P < .001 for each). Together, they accounted for 36% of variance observed., Conclusions: Biallelic USH2A variants were associated with a large range of FV, yet similar in ARRP and USH2, despite hearing loss in USH2. The modified VALVVFQ-48 we evaluated is not ideal for detecting the impact of USH2A-associated retinal degenerations on activities of daily living., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Competing Interests: C.Y.W. is a consultant for Allergan/AbbVie, Regeneron, REGENXBIO, DORC, Genentech, Novartis, Alcon, Alimera Sciences, Opthea, EyePoint Pharmaceuticals, Apellis Pharmaceuticals, and Iveric Bio. The remaining authors declare that they have no conflicts of interest to disclose.

Competing Interests: The authors disclose the following relationships outside of the submitted work: SMK: Ocuphire (consultant); CYW: Allergan/AbbVie, Alcon, DORC, Novartis, Alimera Sciences, Genentech, Apellis, Iveric Bio, EyePoint, Regeneron, REGENXBIO (consultant); AGTC, Alimera Sciences, DRCR Retina Network (research); Springer Publishers (royalties). The remaining author declares that he has no conflicts of interest to disclose.

Competing Interests: The authors report no conflicts of interest directly pertaining to the material presented. C.Y.W. discloses the following relationships outside of the submitted work: Allergan/AbbVie, Alcon, DORC, Novartis, Alimera Sciences, Genentech, Apellis, Iveric Bio, EyePoint, Regeneron, REGENXBIO (consultant); AGTC, Alimera Sciences, DRCR Retina Network (research); Springer Publishers (royalties). The remaining authors declare that they have no conflicts of interest to disclose.

Competing Interests: C.Y.W.: Allergan/AbbVie, Regeneron, REGENXBIO, DORC, Genentech, Novartis, Alcon, Alimera Sciences, Opthea, EyePoint Pharmaceuticals, Apellis Pharmaceuticals, Iveric Bio (consultant for all); AGTC, Alimera Sciences, DRCR Retina Network (research for all); Springer Publishers (royalties). D.S.W.T.: AbbVie, Carl Zeiss, Alcon, Novartis, Bayer, Genentech/Roche, Ocutrx (consultant for all); EyRIS Pte. Ltd. (patent holder). The remaining author declares that he has no conflicts of interest to disclose.

Competing Interests: C.Y.W. discloses the following relationships outside of the submitted work: Allergan/AbbVie, Alcon, DORC, Novartis, Alimera Sciences, Genentech, Apellis, Iveric Bio, EyePoint, Regeneron, REGENXBIO (consultant); AGTC, Alimera Sciences, DRCR Retina Network (research); Springer Publishers (royalties). The remaining authors declare that they have no conflicts of interest to disclose.

Objective: The ultrasonic diagnosis of cervical and facial cystic masses, as well as cases of missed diagnosis and misdiagnosis, was examined, to improve the diagnosis of branchial cleft anomalies., Methods: A retrospective analysis was conducted on 17 patients with branchial cleft cyst anomalies, including 11 males and 6 females, aged 12-53 years, with an average age of 33 ± 2 years, were unilateral single. All patients who underwent an ultrasound examination and image storage for retrospective analysis, and both longitudinal and transverse sections were scanned to observe the shape, size, boundary, peripheral relationship, and blood flow signal of the masses. All cases were examined with an enhanced CT scan, and pathological reports were generated., Results: Among the 17 cases of branchial cleft anomalies, 15 cases were branchial cleft cysts, while one case involved fistula formation and one case involved sinus tract formation. Based on the type of branchial cleft, the first, second, and third cysts were classified in 4, 12, and 1 case, respectively. The sensitivity rate and specificity of ultrasonic diagnosis were 14/17 (82.4%) and 4/6 (66.7%), respectively. Ultrasonic characteristic analysis for the masses can be found in simple cystic masses or hypoechoic masses, most of them are of a regular shape and have a distinct boundary, and almost no blood flow signal. All patients who were misdiagnosed exhibited blood flow signals, including 1 patient with an abundant blood flow signal, 1 patient suspected of having ectopic thyroid with an abnormal function due to the rat-tail sign, 2 patients misdiagnosed as local inflammatory focus, and 1 patient misdiagnosed with tuberculous lymphadenitis., Conclusion: Ultrasound has a detection rate of up to 100% for cervical and facial masses, providing a fundamental determination of lesion characteristics and specific guidance for preoperative diagnosis. If the blood flow signals can be identified and carefully considered their peripheral relationship, the diagnostic rate can be improved., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A novel mesophilic, hydrogenotrophic methanogen, strain CYW5 T , was isolated from a sediment sample of a piston core collected from submarine mud volcano MV5 located in the offshore area of southwestern Taiwan. Cells of strain CYW5 T were irregular coccids, 0.5-1.0 µm in diameter and lysed easily by 0.01 % sodium dodecyl sulphate (SDS) treatment. Strain CYW5 T utilized formate or hydrogen plus carbon dioxide as catabolic substrates for methanogenesis. The optimal growth conditions were 37 °C, 0.043-0.085 M NaCl and pH 6.02-7.32. The genomic DNA G+C content calculated from the genome sequence of strain CYW5 T was 56.2 mol%. The results of phylogenetic analysis of 16S rRNA gene sequences indicated that strain CYW5 T represented a member of the family Methanomicrobiaceae in the order Methanomicrobiales , and was closely related to the members of the genus Methanogenium . The most closely related species was Methanogenium cariaci JR1 T (94.9 % of 16S rRNA gene sequence identity). The average nucleotide identity and average amino acid identity values between strain CYW5 T and members of the family Methanomicrobiaceae were 74.7-78.5 % and 49.1-64.9%, respectively. Although many of the morphological and physiological characteristics of strain CYW5 T and the species of the genus Methanogenium were similar, they were distinguishable by the differences in genomic G+C content and temperature, NaCl and pH ranges for growth. Based on these phenotypic, phylogenetic and genomic results, we propose that strain CYW5 T represents a novel species, of a novel genus, named Methanovulcanius yangii gen. nov., sp. nov. The type strain is CYW5 T (=BCRC AR10048 T =DSM 100756 T =NBRC 111404 T ).

Neovascular age-related macular degeneration (nAMD) leads to irreversible central vision loss if untreated. Frequent administration of anti-vascular endothelial growth factor (anti-VEGF) injections inhibits disease activity with excellent functional and morphological benefits. However, these injections pose a heavy therapeutic burden, and treatment discontinuation is common. Although current anti-VEGF treatment paradigms, such as treat-and-extend, mitigate treatment burden while still leading to acceptable vision outcomes, they fail to sustain initial vision gains for many. Novel longer-acting anti-VEGF therapies may reduce the overall burden on nAMD patients. Gene therapy might offer a paradigm shift by providing continuous expression of anti-VEGF, potentially decreasing treatment requirements and improving long-term vision outcomes. [ Ophthalmic Surg Lasers Imaging Retina 2023;54:654-659.] .

Objective: This study investigated the association between Type D personality and prognoses in stable coronary artery disease (CAD) patients by mode of endpoints, age, and methodological debates to explain substantial heterogeneity among Type D studies., Design: The prospective study was designed to recruit 590 stable CAD patients in Taiwan. Main outcome measures: Demographic and clinical characteristics, and the 14-item Type D scale-Taiwanese version were recorded at discharge., Results: Hierarchical logistic regression analyses showed, regardless of the methodological debates, Type D personality was significantly associated with MACEs though not non-cardiac outcomes in stable CAD patients after adjusting for possible confounders. Furthermore, Type D personality was especially associated with MACEs in stable CAD patients with younger age (<65 y), rather than older age (≥65 y). Subgroup analysis also showed the adverse effect of Type D personality on MACEs was larger among males, those living in the rural region, those with PTCA or stent, those with heart failure, hypertension, diabetes, and those who were smokers., Conclusions: Regardless of whether the methodological debate is dichotomous or continuous, Type D personality was significantly associated with MACEs in stable CAD patients, some of whom had younger age, were males, smokers, or had comorbidities.

Background/purpose: The purpose of this study was to report a young immunocompetent patient with primary central nervous system and vitreoretinal lymphoma initially presenting with peripheral retinitis., Methods: This study is a case report., Results: A 31-year-old woman presented with 20/60 vision in her left eye, vitreous haze, and peripheral retinal whitening. Intravitreal and oral antivirals were initiated for presumed acute retinal necrosis. Anterior chamber paracentesis was negative for viral nucleotide. Subretinal infiltrates developed, and vitreous biopsy was performed and interpreted as "negative except for rare yeast." Antifungal therapy was initiated. She developed multiple unilateral cranial neuropathies with multifocal areas of enhancement on neuroimaging. Lumbar puncture cytology was negative for neoplastic cells. After further worsening, aforementioned specimens were sent to a specialized ophthalmic pathology laboratory and the diagnosis revised to lymphoma of the diffuse B-cell type. Initial disease regression was seen after combined systemic and intraocular chemotherapy; unfortunately, the patient suffered a central nervous system recurrence and died from systemic complications 1 year later., Conclusion: There has been an increased incidence of primary central nervous system and vitreoretinal lymphoma in young patients. Although vitreous biopsy is the diagnostic gold standard for vitreoretinal lymphoma, a risk of false negative interpretation exists. A high index of suspicion and expert interpretation of pathology may be necessary to secure the correct diagnosis.

Background: Remote reporting is an important preventive measure against coronavirus disease 2019 (COVID-19) for radiology departments; it reduces the chance of cross-infections between coworkers. The purpose of this study was to evaluate how the preferred locations that radiologists filed reports from changed in response to COVID-19 by measuring the use of internal teleradiology workstations., Methods: Data were obtained from the radiological information system (RIS) database at our institution, which recorded the reporting workstation for each radiological examination. The reporting activities in 2021 were divided into computed radiography (CR) and computed tomography (CT)/magnetic resonance imaging (MRI) groups. The Wilcoxon signed-rank test was used to measure differences in the use of off-site workstations in prepandemic, midpandemic, and postpandemic periods., Results: There were statistically significant increases in the number of reports filed from off-site workstations for each attending physician from the prepandemic period to the midpandemic period in both the CR (15.1%-25.4%, p = 0.041) and CT/MRI (18.9%-28.7%, p = 0.006) groups. There was no significant difference noted between the prepandemic and postpandemic periods for either the CR (15.1% vs 18.4%, p = 0.727) or CT/MRI group (18.9% vs 23.3%, p = 0.236)., Conclusion: In response to the COVID-19 outbreak, radiologists used internal teleradiology to report CR and CT/MRI examinations significantly more frequently. In contrast to the predictions of previous studies, the use of internal teleradiology returned to baseline levels after the pandemic was under control., Competing Interests: Conflicts of interest: Dr Tzeng-Ji Chen, an editorial board member at Journal of the Chinese Medical Association, had no role in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2023, the Chinese Medical Association.)

Purpose of Review: With frequent antivascular endothelial growth factors (VEGF) injections well established as the standard of care in neovascular age-related macular degeneration (nAMD), focus has now shifted towards decreasing treatment burden without compromising safety and efficacy. This review summarizes clinical stage and recently approved drugs and devices for nAMD, with an emphasis paid to safety concerns and their implications for product adoption., Recent Findings: Three strategies have emerged to decrease the treatment burden associated with the current standard of care: more durable intravitreal agents, sustained-release modalities and gene therapy. The appearance of biosimilars will further impact drug availability and cost. As patterns of adverse events emerge from clinical trial or postmarketing surveillance data, manufacturers have proactively responded by appointing independent review committees or issuing voluntary recalls. However, the example of one biosimilar approved outside of the USA and European Union demonstrates how early safety concerns, even when addressed by substantive data, can generate lingering uncertainty., Summary: As the number of promising new treatments in nAMD continues to grow, so too does the amount of data that providers must sift through. The perception of safety surrounding first movers in each new therapeutic area is sure to affect adoption of that modality more broadly., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Depression is a severe mental disorder, with approximately 300 million people suffering from it. Recent studies have demonstrated that chronic neuroinflammation is significantly associated with intestinal flora and barrier function in depression. As a therapeutic herb, garlic ( Allium sativum L.) has detoxification, antibacterial activity, and antiinflammatory functions; however, its antidepressant effect through gut microbiota and barrier function has not been reported yet. The present study investigated the effect of garlic essential oil (GEO) and its active constituent diallyl disulfide (DADS) on depressive behavior by attenuating the NLRP3 inflammasome, alternating intestinal barrier function and gut microbiota in an unpredictable chronic mild stress (US) model in rats. This study found that dopamine and serotonin turnover rates were reduced significantly with a low dose of GEO (25 mg per kg bw). The GEO groups effectively reversed sucrose preference and increased the total distance traveled in the behavioral test. Moreover, 25 mg per kg bw GEO inhibited the UCMS-induced activated inflammatory response, reflected by reduced expression in the frontal cortex of NLRP3, ASC, caspase-1, and its downstream IL-1β proteins, as well as the concentration of IL-1β and TNF-α in the serum. Supplementation with GEO increased the expression of occludin and ZO-1 and the concentration of short-chain fatty acids to influence the impact of intestinal permeability in depressive conditions. The results revealed that GEO administration caused significant changes in the α and β diversity and abundance of certain bacteria. At the genus level, GEO administration significantly increased the relative abundance, particularly beneficial SCFA-producing bacteria, and may improve depression-like behavior. In conclusion, these results indicated the antidepressant effects of GEO involved in the inflammatory pathway, short-chain fatty acids, intestinal integrity, and intestinal composition.

Diabetic retinopathy (DR), a leading cause of vision loss in working-age adults, induces mosaic patterns of vasculopathy that may be associated with spatial heterogeneity of intraretinal endothelial cells. We recently reported that secretogranin III (Scg3), a neuron-derived angiogenic and vascular leakage factor, selectively binds retinal vessels of diabetic but not healthy mice. Here, we investigated endothelial heterogeneity of three retinal vascular plexuses in DR pathogenesis and the therapeutic implications. Our unique in vivo ligand binding assay detected a 22.7-fold increase in Scg3 binding to retinal vessels of diabetic mice relative to healthy mice. Functional immunohistochemistry revealed that Scg3 predominantly binds to the DR-stressed CD31 - deep retinal vascular plexus but not to the relatively healthy CD31 + superficial and intermediate plexuses within the same diabetic retina. In contrast, VEGF bound to healthy and diabetic retinal vessels indiscriminately with low activity. FITC-dextran assays indicated that selectively increased retinal vascular leakage coincides with Scg3 binding in diabetic mice that was independent of VEGF, whereas VEGF-induced leakage did not distinguish between diabetic and healthy mice. Dose-response curves showed that the anti-Scg3 humanized antibody (hAb) and anti-VEGF aflibercept alleviated DR leakage with equivalent efficacies, and that the combination acted synergistically. These findings suggest: (i) the deep plexus is highly sensitive to DR; (ii) Scg3 binding to the DR deep plexus coincides with the loss of CD31 and compromised endothelial junctions; (iii) anti-Scg3 hAb alleviates vascular leakage by selectively targeting the DR-stressed deep plexus within the same diabetic retina; (iv) combined anti-Scg3 and anti-VEGF treatments synergistically ameliorate DR through distinct mechanisms.

Purpose: To evaluate disease progression using static perimetry (SP) in patients with USH2A-related retinal degeneration, including Usher syndrome type 2 (USH2) and nonsyndromic autosomal recessive retinitis pigmentosa., Design: Prospective, observational cohort study., Methods: A total of 102 patients with biallelic disease-causing sequence variants in USH2A with baseline best-corrected visual acuity (BCVA) letter score ≥54 were recruited from 16 clinical sites in Europe and North America. SP, BCVA, full-field stimulus thresholds, spectral domain optical coherence tomography macular scans, and fundus-guided mesopic microperimetry were performed at baseline and annually. The main outcome measures were total hill of vision (V TOT ), hill of vision in the central 30° (V 30 ), V TOT minus V 30 (V PERIPH ), and mean sensitivity., Results: The average decline (95% CI) was 2.05 (1.40, 2.70) decibel-steradian (dB-sr)/y for V TOT , 0.48 (0.32, 0.65) dB-sr/y for V 30 , 1.53 (0.97, 2.08) dB-sr/y for V PERIPH , and 0.55 (0.40, 0.71) dB/y for mean sensitivity. Average percentage decline per year was 8.3 (5.5, 11.1) for V TOT , 5.2 (3.0, 7.4) for V 30 , 16.0 (9.5, 22.0) for V PERIPH , and 5.1 (3.5, 6.7) for mean sensitivity. Changes from baseline to year 2 in all SP measures were highly correlated (r's ranging from 0.52 [V 30 vs V PERIPH ] to 0.98 [V TOT vs V PERIPH ])., Conclusions: Quantitative measures of SP declined significantly over 2 years in USH2A-related retinal degeneration. The annual percentage rate of change was greatest for V TOT and V PERIPH , whereas V 30 and mean sensitivity changed least, reflecting earlier and more severe peripheral degeneration compared with central loss., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Although teleretinal imaging has proved effective in increasing population-level screening for diabetic retinopathy (DR), there is a lack of quantitative understanding of how to incorporate teleretinal imaging into existing screening guidelines. We develop a mathematical model to determine personalized DR screening recommendations that utilize teleretinal imaging and evaluate the cost-effectiveness of the personalized screening policy., Design: A partially observable Markov decision process is employed to determine personalized screening recommendations based on patient compliance, willingness to pay, and A1C level. Deterministic sensitivity analysis was conducted to evaluate the impact of patient-specific factors on personalized screening policy. The cost-effectiveness of identified screening policies was evaluated via hidden-Markov chain Monte Carlo simulation on a data-based hypothetical cohort., Participants: Screening policies were simulated for a hypothetical cohort of 500 000 patients with parameters based on the literature and electronic medical records of 2457 patients who received teleretinal imaging from 2013 to 2020 from the Harris Health System., Methods: Population-based mathematical modeling study. Interventions included dilated fundus examinations referred to as clinical screening, teleretinal imaging, and wait and watch recommendations., Main Outcome Measures: Personalized screening recommendations based on patient-specific factors. Accumulated quality-adjusted life-years (QALYs) and cost (USD) per patient under different screening policies. Incremental cost-effectiveness ratio to compare different policies., Results: For the base cohort, on average, teleretinal imaging was recommended 86.7% of the time over each patient's lifetime. The model-based personalized policy dominated other standardized policies, generating more QALY gains and cost savings for at least 57% of the base cohort. Similar outcomes were observed in sensitivity analyses of the base cohort and the Harris Health-specific cohort and rural population scenario analysis., Conclusions: A mathematical model was developed as a decision support tool to identify a personalized screening policy that incorporates both teleretinal imaging and clinical screening and adapts to patient characteristics. Compared with current standardized policies, the model-based policy significantly reduces costs, whereas it is performing comparably, if not better, in terms of QALY gain. A personalized approach to DR screening has significant potential benefits that warrant further exploration., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright © 2023 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

In this work, the ultrathin two-dimensional (2D) indium oxide (InO x ) with a large area of more than 100 μm 2 and a high degree of uniformity was automatically peeled off from indium by the liquid-metal printing technique. Raman and optical measurements revealed that 2D-InO x has a polycrystalline cubic structure. By altering the printing temperature which affects the crystallinity of 2D-InO x , the mechanism of the existence and disappearance of memristive characteristics was established. The tunable characteristics of the 2D-InO x memristor with reproducible one-order switching was manifest from the electrical measurements. Further adjustable multistate characteristics of the 2D-InO x memristor and its resistance switching mechanism were evaluated. A detailed examination of the memristive process demonstrated the Ca 2+ mimic dynamic in 2D-InO x memristors as well as the fundamental principles underlying biological and artificial synapses. These surveys allow us to comprehend a 2D-InO x memristor using the liquid-metal printing technique and could be applied to future neuromorphic applications and in the field of revolutionary 2D material exploration.

In this era of rapid information exchange in public networks, there is a risk to information security. Data hiding is an important technique for privacy protection. Image interpolation is an important data-hiding technique in image processing. This study proposed a method called neighbor mean interpolation by neighboring pixels (NMINP) that calculates a cover image pixel by neighbor mean interpolation and neighboring pixels. To reduce image distortion, NMINP limits the number of bits when embedding secret data, making NMINP have a higher hiding capacity and peak signal-to-noise ratio (PSNR) than other methods. Furthermore, in some cases, the secret data are flipped, and the flipped data are treated in ones' complement format. A location map is not needed in the proposed method. Experimental results comparing NMINP with other state-of-the-art methods show that NMINP improves the hiding capacity by more than 20% and PSNR by 8%.

Importance: Retinopathy of prematurity (ROP) is a potentially blinding retinal disease with poorly defined epidemiology. Understanding of which infants are most at risk for developing ROP may foster targeted detection and prevention efforts., Objective: To identify changes in ROP incidence in the US from 2003 to 2019., Design, Setting, and Participants: This retrospective database cohort study used the Healthcare Cost and Utilization Project Kids' Inpatient Databases. These nationwide databases are produced every 3 years, include data from over 4000 hospitals, and are designed to generate national estimates of health care trends in the US. Participants included pediatric newborns at risk for ROP development between 2003 and 2019. Data were analyzed from September 30, 2021, to January 13, 2022., Exposures: Premature or low-birth-weight infants with relevant International Classification of Diseases, Ninth Revision or Tenth Revision codes were considered ROP candidates. Infants with ROP were identified using relevant codes., Main Outcomes and Measures: ROP incidence in selected subpopulations (based on database-reported race and ethnicity, sex, location, income) was measured. To determine whether incidences varied across time or subpopulations, χ2 tests of independence were used., Results: This study included 125 212 ROP discharges (64 715 male infants [51.7%]) from 23 187 683 births. The proportion of premature infants diagnosed with ROP increased from 4.4% (11 720 of 265 650) in 2003 to 8.1% (27 160 of 336 117) in 2019. Premature infants from the lowest median household income quartile had the greatest proportional increase of ROP diagnoses from 4.9% (3244 of 66 871) to 9.0% (9386 of 104 235; P < .001). Premature Black infants experienced the largest increase from 5.8% (2124 of 36 476) to 11.6% (7430 of 63 925; P < .001) relative to other groups (2.71%; 95% CI, 2.56%-2.87%; P < .001). Hispanic infants experienced the second largest increase from 4.6% (1796 of 39 106) to 8.2% (4675 of 57 298; P < .001) relative to other groups (-0.16%; 95% CI, -0.29% to -0.03%; P = .02). The Southern US experienced the greatest proportional growth of ROP diagnoses, increasing from 3.7% (3930 of 106 772) to 8.3% (11 952 of 144 013; P < .001) relative to other groups (1.61%; 95% CI, 1.51%-1.71%; P < .001). ROP diagnoses proportionally increased in urban areas and decreased in rural areas., Conclusions and Relevance: This cohort study found that ROP incidence among premature infants increased from 2003 to 2019, especially among Black and Hispanic infants. Infants from the lowest-income areas persistently had the highest proportional incidence of ROP, and all regions experienced a significant increase in ROP incidence with the most drastic changes occurring in the South. These trends suggest that ROP is a growing problem in the US and may be disproportionately affecting historically marginalized groups.

Objectives: Ferroptosis is a newly discovered cell death mode that has been confirmed to occur in the intestinal epithelial cells in ulcerative colitis (UC). In this study we aimed to elucidate the mechanism of ferroptosis and its association with adenosine monophosphate-activated protein kinase (AMPK) in UC., Methods: Gene expression profiles of colonic mucosa (GSE87473) were downloaded. Both human colonic samples and dextran sodium sulfate (DSS)-induced colitis murine model were used. The molecular markers of ferroptosis were detected using western blot and immunohistochemistry. Symptoms, iron abundance, and lipid peroxidation level of the mouse model were measured to evaluate the role of AMPK activation in ferroptosis., Results: Both gene and protein expressions of GPX4 and FTH1 were decreased in UC patients compared with the healthy controls. An increased iron abundance and lipid peroxidation level in colon tissues and damaged mitochondria were found in DSS-induced colitis. AMPK expression was decreased in UC patients and correlated with FTH1 and GPX4. Activation of AMPK with metformin inhibited ferroptosis in the colon, improved symptoms, and prolonged the lifespan in DSS-induced colitis mice., Conclusions: Ferroptosis can be observed in colonic tissues in UC. AMPK activation inhibits ferroptosis in murine colitis model, which may act as a potential target for the treatment of colitis., (© 2023 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Objectives: This study investigated the effects of outpatient rehabilitation therapy (RT) on the functional performance of children from Eastern Taiwan with rare or genetic diseases., Materials and Methods: This retrospective observational cohort study included 73 children from Eastern Taiwan who were affected with rare or genetic diseases, with an average age of 8.57 ± 5.33 years (47 boys and 26 girls). Each child received the goal-directed therapy known as outpatient RT, which was delivered by a multidisciplinary team of specialists. To assess the effectiveness of RT, the WeeFIM-C questionnaire data were collected and analyzed., Results: After receiving outpatient RT, most of the children only required low-to-moderate assistance with self-care tasks (4.36 ± 2.38), and they could perform mobility-related activities under supervision or independently (5.70 ± 2.29). Moreover, most only required minimal assistance with tasks related to cognitive functioning and tended to complete such tasks under supervision (4.97 ± 2.05). The functional performance was significantly different among three studied groups, in terms of self-care ( F [2, 68] = 5.42, P < 0.007), mobility ( F [2, 68] = 8.17, P < 0.001), cognitive functioning ( F [2, 68] = 3.31, P < 0.042), and overall ( F [2, 68] = 6.44, P < 0.003) functional performance., Conclusion: The results of this study demonstrated that the functional status was different among three studied groups in terms of self-care, mobility, and cognitive functioning after receiving outpatient RT., Competing Interests: Dr. Shao-Yin Chu, an editorial board members at Tzu Chi Medical Journal, had no role in the peer review process of or decision to publish this article. The other authors declared no conflicts of interest in writing this paper., (Copyright: © 2023 Tzu Chi Medical Journal.)

Carbonyl reductase (CR)-catalyzed bioreduction in the organic phase and the neat substrate reaction system is a lasting challenge, placing higher requirements on the performance of enzymes. Protein engineering is an effective method to enhance the properties of enzymes for industrial applications. In the present work, a single point mutation E145A on our previously constructed carbonyl reductase mutant LsCR M3 , co-evolved thermostability, and activity. Compared with LsCR M3 , the catalytic efficiency k cat /K M of LsCR M3 -E145A (LsCR M4 ) was increased from 6.6 s -1 ∙mM -1 to 21.9 s -1 ∙mM -1 . Moreover, E145A prolonged the half-life t 1/2 at 40 °C from 4.1 h to 117 h, T m was increased by 5 °C, T 50 30 was increased by 14.6 °C, and T opt was increased by 15 °C. Only 1 g/L of lyophilized E. coli cells expressing LsCR M4 completely reduced up to 600 g/L 2-chloro-1-(3,4-difluorophenyl)ethanone (CFPO) within 13 h at 45°C, yielding the corresponding (1S)-2-chloro-1-(3,4-difluorophenyl)ethanol ((S)-CFPL) in 99.5% ee P , with a space-time yield (STY) of 1.0 kg/L∙d, the substrate to catalyst ratios (S/C) of 600 g/g. Compared with LsCR M3 , the substrate loading was increased by 50%, with the S/C increased by 14 times. Compared with LsCR WT , the substrate loading was increased by 6.5 times. In contrast, LsCR M4 completely converted 600 g/L CFPO within 12 h in the neat substrate bioreaction system (NSBRS). This article is protected by copyright. All rights reserved., (This article is protected by copyright. All rights reserved.)

Background: Reporting the findings from radiologic images is an important method for radiologists to communicate with referring physicians. The purpose of this study was to evaluate the effectiveness of the recommendations for additional imaging (RAIs) after abdominal computed tomography (CT) studies for abdominal magnetic resonance (MR) imaging., Methods: The institutional review board approved this retrospective study, which includes data collected from the radiology information system (RIS) database of a tertiary medical referral center. Associations between abdominal CT and subsequent abdominal MR were recorded. The effectiveness of RAIs in an abdominal report was determined. The influence of the wording and the location of the RAIs were also analyzed., Results: The presence of RAIs in an abdominal CT report for an abdominal MR examination was more likely to result in a subsequent MR examination within 120 days (36.7% vs. 4.0%). RAIs were also associated with a reduction in the time interval between the CT and MR examinations (29.0 days vs. 39.0 days). The most effective recommendations included wording that advocated for further evaluation and were mentioned in both the context and conclusion of the report., Conclusion: RAIs have a significant influence on clinical decisions. Radiologists should be aware of the power of RAIs and be prudent and conscientious when making recommendations in radiology reports., Competing Interests: Conflicts of interest: Dr. Tzeng-Ji Chen, an editorial board member at Journal of the Chinese Medical Association , had no role in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2022, the Chinese Medical Association.)