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COMPARISON OF THE EFFICACY AND SAFETY OF RANIBIZUMAB 0.5 MG VERSUS 1.0 MG WITH PARS PLANA VITRECTOMY FOR THE TREATMENT OF PROLIFERATIVE DIABETIC RETINOPATHY: A Randomized Controlled Trial.
Su, T, Lai, D, Wu, Y, Gu, C, He, S, Meng, C, Cai, C, Zhang, J, Luo, D, Chen, J, et al
Retina (Philadelphia, Pa.). 2024;(4):680-688
Abstract
PURPOSE To investigate the effectiveness of two regimens of ranibizumab-assisted pars plana vitrectomy in the treatment of patients with proliferative diabetic retinopathy. METHODS This is a prospective, 6-month, randomized controlled trial. Eighty patients with 87 eyes requiring pars plana vitrectomy treatment for proliferative diabetic retinopathy were included and randomly divided into a 1.0-mg injection group and a 0.5-mg injection group. The ranibizumab was delivered intraoperatively, at the close of surgery. The vitreous hemorrhage grade, best-corrected visual acuity, central macular thickness, and safety data were assessed to Month 6. RESULTS The 1.0-mg injection group had a milder grade and a lower reoccurrence rate of early postoperatively vitreous hemorrhage than the 0.5-mg injection group (35.0% and 63.4%, respectively, P = 0.0195). The mean best-corrected visual acuity of two groups was significantly improved from baseline to 6 months after surgery, 1.60 ± 0.72 Logarithm of the Minimum Angle of Resolution (LogMAR) (<20/200) to 0.47 ± 0.49 LogMAR (20/59) for the 1.0-mg injection group and 1.51 ± 0.69 LogMAR (<20/200) to 0.50 ± 0.31 LogMAR (20/63) for the 0.5-mg injection group, but there was no significant difference between the two groups ( P = 0.74). There was no significant difference in the mean decrease in central macular thickness and probability of postoperative adverse events between the two groups. CONCLUSION Intravitreal injection of 1.0 mg of ranibizumab after pars plana vitrectomy compared with the recommended dose of 0.5 mg significantly reduced the recurrence and severity of early postoperative vitreous hemorrhage in patients with proliferative diabetic retinopathy. It also contributed to the early recovery of visual acuity after surgery and did not increase postoperative adverse events.
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Recent Advances in Search of Bioactive Secondary Metabolites from Fungi Triggered by Chemical Epigenetic Modifiers.
Xue, M, Hou, X, Fu, J, Zhang, J, Wang, J, Zhao, Z, Xu, D, Lai, D, Zhou, L
Journal of fungi (Basel, Switzerland). 2023;(2)
Abstract
Genomic analysis has demonstrated that many fungi possess essential gene clusters for the production of previously unobserved secondary metabolites; however, these genes are normally reduced or silenced under most conditions. These cryptic biosynthetic gene clusters have become treasures of new bioactive secondary metabolites. The induction of these biosynthetic gene clusters under stress or special conditions can improve the titers of known compounds or the production of novel compounds. Among the inducing strategies, chemical-epigenetic regulation is considered a powerful approach, and it uses small-molecule epigenetic modifiers, which mainly act as the inhibitors of DNA methyltransferase, histone deacetylase, and histone acetyltransferase, to promote changes in the structure of DNA, histones, and proteasomes and to further activate cryptic biosynthetic gene clusters for the production of a wide variety of bioactive secondary metabolites. These epigenetic modifiers mainly include 5-azacytidine, suberoylanilide hydroxamic acid, suberoyl bishydroxamic acid, sodium butyrate, and nicotinamide. This review gives an overview on the method of chemical epigenetic modifiers to trigger silent or low-expressed biosynthetic pathways to yield bioactive natural products through external cues of fungi, mainly based on the research progress in the period from 2007 to 2022. The production of about 540 fungal secondary metabolites was found to be induced or enhanced by chemical epigenetic modifiers. Some of them exhibited significant biological activities such as cytotoxic, antimicrobial, anti-inflammatory, and antioxidant activity.
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The Role of Müller Cells in Diabetic Macular Edema.
Lai, D, Wu, Y, Shao, C, Qiu, Q
Investigative ophthalmology & visual science. 2023;(10):8
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Abstract
Diabetic macular edema (DME) is a common complication of diabetic retinopathy and is the leading cause of vision loss in diabetic patients. Various factors, such as metabolic disorders and inflammation caused by hyperglycemia, are involved in the occurrence and development of DME, but the specific mechanism is still unclear. Müller cells are a type of macroglial cell unique to the fundus, distributed throughout the retina, and they play a unique role in retinal homeostasis. This article reviews the role of Müller cells in the pathological process of DME and the research progress in the treatment of DME by targeting Müller cells through gene therapy.
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Recent Advances in Sorbicillinoids from Fungi and Their Bioactivities (Covering 2016-2021).
Hou, X, Zhang, X, Xue, M, Zhao, Z, Zhang, H, Xu, D, Lai, D, Zhou, L
Journal of fungi (Basel, Switzerland). 2022;(1)
Abstract
Sorbicillinoids are a family of hexaketide metabolites with a characteristic sorbyl side chain residue. Sixty-nine sorbicillinoids from fungi, newly identified from 2016 to 2021, are summarized in this review, including their structures and bioactivities. They are classified into monomeric, dimeric, trimeric, and hybrid sorbicillinoids according to their basic structural features, with the main groups comprising both monomeric and dimeric sorbicillinoids. Some of the identified sorbicillinoids have special structures such as ustilobisorbicillinol A, and sorbicillasins A and B. The majority of sorbicillinoids have been reported from fungi genera such as Acremonium, Penicillium, Trichoderma, and Ustilaginoidea, with some sorbicillinoids exhibiting cytotoxic, antimicrobial, anti-inflammatory, phytotoxic, and α-glucosidase inhibitory activities. In recent years, marine-derived, extremophilic, plant endophytic, and phytopathogenic fungi have emerged as important resources for diverse sorbicillinoids with unique skeletons. The recently revealed biological activities of sorbicillinoids discovered before 2016 are also described in this review.
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Multi-response optimization of process parameters in nitrogen-containing gray cast iron milling process based on application of non-dominated ranking genetic algorithm.
Lin, Y, Ma, J, Lai, D, Zhang, J, Li, W, Li, S, He, S
Heliyon. 2022;(11):e11629
Abstract
As a new, high-strength and clean cast iron material, nitrogen-containing gray cast iron has excellent properties and a wide range of application prospects. However, the excellent material properties of the material not only make the machinability challenging, but also the high efficiency and quality of the machining process is a pressing issue. Therefore, it is necessary to study the machining characteristics of nitrogen-containing gray cast iron to obtain the optimal machining parameters to enrich the research work on nitrogen-containing gray cast iron. In this paper, the machining characteristics of nitrogen-containing gray cast iron are systematically studied, and the effects of cutting parameters on milling force, milling temperature, and surface roughness are analyzed. And, based on the machinability assessment, the objective function weights under different production requirements are determined by using hierarchical analysis trade-offs, and an integrated optimization model based on non-dominated ranking genetic algorithm and hierarchical analysis (AHP) is proposed. The model outputs the optimal combination of milling parameters by inputting the cutting speed (vc), feed rate per tooth (fz) and cutting depth (ap), surface roughness and cutting efficiency as the objective functions. The experimental results show that cutting depth has the greatest effect on the cutting force and cutting speed has the greatest effect on the cutting temperature and the surface roughness. The passivation effect of nitrogen on the graphite tip resulted in an increase in both cutting force and cutting temperature. The parameter optimization results indicated that the optimized roughing parameters significantly improve the surface quality while machining efficiently; the optimized finishing parameters improve Ra by 23.53% while ensuring higher MRR, which can achieve efficient and high-quality machining under different production requirements and provide an experimental basis for practical engineering applications of nitrogen-containing gray cast iron.
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A Novel Smart Belt for Anxiety Detection, Classification, and Reduction Using IIoMT on Students' Cardiac Signal and MSY.
Pal, R, Adhikari, D, Heyat, MBB, Guragai, B, Lipari, V, Brito Ballester, J, De la Torre Díez, I, Abbas, Z, Lai, D
Bioengineering (Basel, Switzerland). 2022;(12)
Abstract
The prevalence of anxiety among university students is increasing, resulting in the negative impact on their academic and social (behavioral and emotional) development. In order for students to have competitive academic performance, the cognitive function should be strengthened by detecting and handling anxiety. Over a period of 6 weeks, this study examined how to detect anxiety and how Mano Shakti Yoga (MSY) helps reduce anxiety. Relying on cardiac signals, this study follows an integrated detection-estimation-reduction framework for anxiety using the Intelligent Internet of Medical Things (IIoMT) and MSY. IIoMT is the integration of Internet of Medical Things (wearable smart belt) and machine learning algorithms (Decision Tree (DT), Random Forest (RF), and AdaBoost (AB)). Sixty-six eligible students were selected as experiencing anxiety detected based on the results of self-rating anxiety scale (SAS) questionnaire and a smart belt. Then, the students were divided randomly into two groups: experimental and control. The experimental group followed an MSY intervention for one hour twice a week, while the control group followed their own daily routine. Machine learning algorithms are used to analyze the data obtained from the smart belt. MSY is an alternative improvement for the immune system that helps reduce anxiety. All the results illustrate that the experimental group reduced anxiety with a significant (p < 0.05) difference in group × time interaction compared to the control group. The intelligent techniques achieved maximum accuracy of 80% on using RF algorithm. Thus, students can practice MSY and concentrate on their objectives by improving their intelligence, attention, and memory.
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Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies.
Munn-Chernoff, MA, Johnson, EC, Chou, YL, Coleman, JRI, Thornton, LM, Walters, RK, Yilmaz, Z, Baker, JH, Hübel, C, Gordon, S, et al
Addiction biology. 2021;(1):e12880
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Abstract
Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa and problem alcohol use (genetic correlation [rg ], twin-based = 0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge eating, AN without binge eating, and a bulimia nervosa factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder and schizophrenia. Total study sample sizes per phenotype ranged from ~2400 to ~537 000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder- and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (rg = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN (rg = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating (rg = 0.27; q = 0.0016). Conversely, significant negative genetic correlations were observed between three nondiagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge eating (rgs = -0.19 to -0.23; qs < 0.04). The genetic correlation between AUD and AN was no longer significant after co-varying for major depressive disorder loci. The patterns of association between eating disorder- and substance-use-related phenotypes highlights the potentially complex and substance-specific relationships among these behaviors.
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Efficacy of commercial mouth-rinses on SARS-CoV-2 viral load in saliva: randomized control trial in Singapore.
Seneviratne, CJ, Balan, P, Ko, KKK, Udawatte, NS, Lai, D, Ng, DHL, Venkatachalam, I, Lim, KS, Ling, ML, Oon, L, et al
Infection. 2021;(2):305-311
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Abstract
PURPOSE One of the key approaches to minimize the risk of COVID-19 transmission would be to reduce the titres of SARS-CoV-2 in the saliva of infected COVID-19 patients. This is particularly important in high-risk procedures like dental treatment. The present randomized control trial evaluated the efficacy of three commercial mouth-rinse viz. povidone-iodine (PI), chlorhexidine gluconate (CHX) and cetylpyridinium chloride (CPC), in reducing the salivary SARS-CoV-2 viral load in COVID-19 patients compared with water. METHODS A total of 36 SARS-CoV-2-positive patients were recruited, of which 16 patients were randomly assigned to four groups-PI group (n = 4), CHX group (n = 6), CPC group (n = 4) and water as control group (n = 2). Saliva samples were collected from all patients at baseline and at 5 min, 3 h and 6 h post-application of mouth-rinses/water. The samples were subjected to SARS-CoV-2 RT-PCR analysis. RESULTS Comparison of salivary Ct values of patients within each group of PI, CHX, CPC and water at 5 min, 3 h and 6 h time points did not show any significant differences. However, when the Ct value fold change of each of the mouth-rinse group patients were compared with the fold change of water group patients at the respective time points, a significant increase was observed in the CPC group patients at 5 min and 6 h and in the PI group patients at 6 h. CONCLUSION The effect of decreasing salivary load with CPC and PI mouth-rinsing was observed to be sustained at 6 h time point. Within the limitation of the current study, as number of the samples analyzed, the use of CPC and PI formulated that commercial mouth-rinses may be useful as a pre-procedural rinse to help reduce the transmission of COVID-19. ISRCTN (ISRCTN95933274), 09/09/20, retrospectively registered.
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Design and rationale of the randomized trial of comprehensive lifestyle modification, optimal pharmacological treatment and utilizing PET imaging for quantifying and managing stable coronary artery disease (the CENTURY study).
Kitkungvan, D, Johnson, NP, Kirkeeide, R, Haynie, M, Carter, C, Patel, MB, Bui, L, Madjid, M, Mendoza, P, Roby, AE, et al
American heart journal. 2021;:135-146
Abstract
BACKGROUND The literature reports no randomized trial in chronic coronary artery disease (CAD) of a comprehensive management strategy integrating intense lifestyle management, maximal medical treatment to specific goals and high precision quantitative cardiac positron emission tomography (PET) for identifying high mortality risk patients needing essential invasive procedures. We hypothesize that this comprehensive strategy achieves greater risk factor reduction, lower major adverse cardiovascular events and fewer invasive procedures than standard practice. METHODS The CENTURY Study (NCT00756379) is a randomized-controlled-trial study in patients with stable or at high risk for CAD. Patients are randomized to standard of care (Standard group) or intense comprehensive lifestyle-medical treatment to targets and PET guided interventions (Comprehensive group). Comprehensive Group patients are regularly consulted by the CENTURY team implementing diet/lifestyle/exercise program and medical treatment to target risk modification. Cardiac PET at baseline, 24-, and 60-months quantify the physiologic severity of CAD and guide interventions in the Comprehensive group while patients and referring physicians of the Standard group are blinded to PET results. The primary end-point is the CENTURY risk score reduction during 5 years follow-up. The secondary endpoint is a composite of death, non-fatal myocardial infarction, stroke, and coronary revascularization. CONCLUSIONS The CENTURY Study is the first study in stable CAD to test the incremental benefit of a comprehensive strategy integrating intense lifestyle modification, medical treatment to specific goals, and high-precision quantitative myocardial perfusion imaging to guide revascularization. A total of 1028 patients have been randomized, and the 5 years follow-up will conclude in 2022.
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Effects of reverse genetic mutations on the spectral and photochemical behavior of a photoactivatable fluorescent protein PAiRFP1.
Hassan, F, Khan, FI, Song, H, Lai, D, Juan, F
Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy. 2020;:117807
Abstract
Bacteriophytochrome photoreceptors (BphPs) containing biliverdin (BV) have great potential for the development of genetically engineered near-infrared fluorescent proteins (NIR FPs). We investigated a photoactivatable fluorescent protein PAiRFP1, was engineered through directed molecular evolution. The coexistence of both red light absorbing (Pr) and far-red light absorbing (Pfr) states in dark is essential for the photoactivation of PAiRFP1. The PCR based site-directed reverse mutagenesis, spectroscopic measurements and molecular dynamics (MD) simulations were performed on three targeted sites V386A, V480A and Y498H in PHY domain to explore their potential effects during molecular evolution of PAiRFP1. We found that these substitutions did not affect the coexistence of Pr and Pfr states but led to slight changes in the photophysical parameters. The covalent docking of biliverdin (cis and trans form) with PAiRFP1 was followed by several 100 ns MD simulations to provide some theoretical explanations for the coexistence of Pr and pfr states. The results suggested that experimentally observed coexistence of Pr and Pfr states in both PAiRFP1 and mutants were resulted from the improved stability of Pr state. The use of experimental and computational work provided useful understanding of Pr and Pfr states and the effects of these mutations on the photophysical properties of PAiRFP1.