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Faricimab is a bispecific antibody that acts through dual inhibition of both angiopoietin-2 and vascular endothelial growth factor A. We report primary results of two phase 3 trials evaluating intravitreal faricimab with extension up to every 16 weeks for neovascular age-related macular degeneration (nAMD).TENAYA and LUCERNE were randomised, double-masked, non-inferiority trials across 271 sites worldwide. Treatment-naive patients with nAMD aged 50 years or older were randomly assigned (1:1) to intravitreal faricimab 6·0 mg up to every 16 weeks, based on protocol-defined disease activity assessments at weeks 20 and 24, or aflibercept 2·0 mg every 8 weeks. Randomisation was performed through an interactive voice or web-based response system using a stratified permuted block randomisation method. Patients, investigators, those assessing outcomes, and the funder were masked to group assignments. The primary endpoint was mean change in best-corrected visual acuity (BCVA) from baseline averaged over weeks 40, 44, and 48 (prespecified non-inferiority margin of four letters), in the intention-to-treat population. Safety analyses included patients who received at least one dose of study treatment. These trials are registered with ClinicalTrials.gov (TENAYA NCT03823287 and LUCERNE NCT03823300).Across the two trials, 1329 patients were randomly assigned between Feb 19 and Nov 19, 2019 (TENAYA n=334 faricimab and n=337 aflibercept), and between March 11 and Nov 1, 2019 (LUCERNE n=331 faricimab and n=327 aflibercept). BCVA change from baseline with faricimab was non-inferior to aflibercept in both TENAYA (adjusted mean change 5·8 letters [95% CI 4·6 to 7·1] and 5·1 letters [3·9 to 6·4]; treatment difference 0·7 letters [-1·1 to 2·5]) and LUCERNE (6·6 letters [5·3 to 7·8] and 6·6 letters [5·3 to 7·8]; treatment difference 0·0 letters [-1·7 to 1·8]). Rates of ocular adverse events were comparable between faricimab and aflibercept (TENAYA n=121 [36·3%] vs n=128 [38·1%], and LUCERNE n=133 [40·2%] vs n=118 [36·2%]).Visual benefits with faricimab given at up to 16-week intervals demonstrates its potential to meaningfully extend the time between treatments with sustained efficacy, thereby reducing treatment burden in patients with nAMD.F Hoffmann-La Roche.

It has been suggested that the coronavirus disease 2019 (COVID-19) pandemic has had a negative impact on glycemic control in patients with type 2 diabetes mellitus (T2DM). However, no study has examined yearly trends in glycated hemoglobin (HbA1c) levels after the start of the COVID-19 outbreak. Here, we performed a retrospective analysis of HbA1c concentrations during the early period of the COVID-19 outbreak (COVID-19 cohort) and then compared the yearly trend in the mean HbA1c level, along with fluctuations in HbA1c levels, with those during previous years (non-COVID-19 cohorts). We observed that the mean HbA1c level in patients with T2DM increased during the first 6 months of the COVID-19 outbreak. After 6 months, HbA1c levels in the COVID-19 cohort returned to levels seen in the non-COVID-19 cohorts. The data suggest that vulnerable patients with T2DM should be monitored closely during the early period of a pandemic to ensure they receive appropriate care.

A new accepter unit, 2,3-didodecyl-6,7-difluoroquinoxaline, was prepared and utilized for the synthesis of electron acceptor–donor–acceptor materials for organic solar cells. 2,3-Didodecyl-6,7-difl...

In this study, a simple approach was described to investigate the theoretical models for electrospun polymer nanofiber-reinforced nanocomposites. For predicting the tensile strength of the electrospun nylon 6 nanofiber-reinforced polyurethane acrylate composites, conventional Pukanszky, Nicolais–Narkis, Halpin–Tsai, and Neilson models were used, while for Young’s modulus, Halpin–Tsai, modified Halpin–Tsai, and Hui–Shia models were used. As per the Pukanszky model, composite films showed better interaction since the values of the interaction parameter, B, were more than 3. Similarly, the value of an interfacial parameter, K, was less than 1.21 (K = −5, for the curve fitting) as per the Nicolais–Narkis model, which indicated better interfacial interaction. For composite films, the modified Halpin–Tsai model was revised again by introducing the orientation factor, α, which was 0.333 for the randomly oriented continuous nanofiber-reinforced composites, and the exponential shape factor, ξ = (2l/d)e−avf−b, which showed the best agreement with the experimental Young’s modulus results. Based on mentioned remarks, these models would be applicable for estimating the tensile strength and Young’s modulus of electrospun nanofiber-reinforced polymer composite films.

In this study, we focused on the manufacturing of void-free composites of electrospun nylon 6 nanofibers as reinforcement for the poly(vinyl alcohol) (PVA) matrix. PVA solution was introduced into ...

A simple modification of cellulose nanocrystals (CNC) was intended for preparing ameliorated nanofillers for UV-curable PUA coatings. This modification was carried out by dispersing CNC in DMSO wit...

To characterize geographic atrophy (GA) and to evaluate differences between Asians and non-Asians.Retrospective cohort study PARTICIPANTS: Subjects aged ≥50 years with GA secondary to AMD in the absence of neovascularisation in the study eye and follow-up of ≥ 2 years.Multicenter, retrospective case series. GA lesion characterized at baseline and last follow-up based on multimodal imaging (fundus autofluorescence [FAF], near infrared [NIR], SD-OCT). Patients were grouped as either Asian or non-Asian descent.Comparison of 1) phenotypes of GA lesions (size, foveal involvement, number of foci, drusen background, choroid background) and 2) growth rate of GA.A total of 144 patients (169 eyes) with distribution of 50.9% Asians and 49.1% non-Asians. The age and gender were similar between Asians and non-Asians (Asians: mean age 77.2±10.1; 47.9% female; non-Asians: mean age 79.7±8.4; 58.7% female). Asians had thicker choroids (167±74μm vs 134±56μm, p0.01) and lower prevalence of any drusen (40.7% vs 66.3%, p0.01). At baseline, the GA area was smaller in Asians versus non-Asians (NIR 3.7±4.6mm

Neurogenic differentiation factor 1 (NEUROD1) is frequently overexpressed in small-cell lung cancer (SCLC). NEUROD1 plays an important role in promoting malignant behavior and survival. In this study, we evaluated the association between putative functional polymorphisms in 45 NEUROD1 target genes and chemotherapy response and survival outcomes in 261 patients with SCLC. Among the 100 single nucleotide polymorphisms (SNPs) studied, two were significantly associated with both chemotherapy response and overall survival (OS) of patients with SCLC. The SNP rs3806915C>A in semaphorin 6A (SEMA6A) gene was significantly associated with better chemotherapy response and OS (P = 0.04 and P = 0.04, respectively). The SNPrs11265375C>T in nescient helix-loop helix 1 (NHLH1) gene was also associated with better chemotherapy response and OS (P = 0.04 and P = 0.02, respectively). Luciferase assay showed a significantly higher promoter activity of SEMA6A with the rs3806915 A allele than C allele in H446 lung cancer cells (P = 4 × 10-6). The promoter activity of NHLH1 showed a significantly higher with the rs11265375 T allele than C allele (P = 0.001). These results suggest that SEMA6A rs3806915C>A and NHLH1 rs11265375C>T polymorphisms affect the promoter activity and expression of the genes, which may affect the survival outcome of patients with SCLC.

Purpose To develop consensus terminology in the setting of polypoidal choroidal vasculopathy (PCV), and to develop and validate a set of diagnostic criteria not requiring indocyanine green angiograph (ICGA) for differentiating PCV from typical neovascular age-related macular degeneration (nAMD) based on a combination of OCT and color fundus photograph findings. Design Evaluation of diagnostic test Participants Panel of retina specialists. Methods As part of the Asia-Pacific Ocular Imaging Society (APOIS), an international group of experts surveyed and discussed the published literature regarding the current nomenclature and lesion components for PCV and proposed an updated consensus nomenclature, which reflects our latest understanding based on imaging and histology reports. The workgroup evaluated a set of diagnostic features based on OCT and color fundus photographs for PCV that may distinguish it from typical nAMD and assessed the performance of individual and combinations of these non-ICGA features, aiming to propose a new set of diagnostic criteria which does not require the use of ICGA. The final recommendation was validated in 80 eyes from 2 additional cohorts. Main Outcome Measures A consensus nomenclature system for PCV lesion components and non-ICGA-based criteria to differentiate PCV from typical nAMD. Results The workgroup recommended the terms ‘polypoidal lesion’ and ‘branching neovascular network’ for the two key lesion components in PCV. For the diagnosis of PCV, the combination of 3 OCT-based ‘major criteria’ (sub-RPE ring-like lesion, enface OCT complex RPE elevation, and sharp-peaked PED) achieved an area under the receiver operating characteristic curve of 0.90. Validation of this new scheme in a separate subset 110 eyes achieved an accuracy of 82%. Conclusions We propose updated terminology for PCV lesion components which better reflect the nature of these lesions which was based on international consensus. A set of practical diagnostic criteria that are easily applied to SD-OCT can be used for diagnosing PCV with high accuracy in clinical settings in which ICGA is not routinely performed.

The control of surface wettability through a combination of surface roughness, chemical composition, and structural modification has attracted significant attention for antifogging and antibacterial applications. Herein, a two-step spin-coating method for amphiphilic organic-inorganic hybrid materials with incorporated transition metal ions is presented. The coating solution was prepared via photochemical thiol-ene click reaction between the mercapto functional group in trimethylolpropane tris(3-mercaptopropionate) and the vinyl functionalized silica precursor 3-(trimethoxysilyl)propyl methacrylate. In the first step of coating, a glass substrate was coated using a solution of metal nitrate hydrates and subsequently showed hydrophobic properties. As the second step, the spin-coated glass substrate was further coated with silica nanoparticles (SiO2 NPs) and polycaprolactone triol (PCT) suspension, where the contents of SiO2 NPs were fixed at 0.1 wt %, unless otherwise noted. The coated substrate exhibited hydrophilic properties. For comparison, the coating was also formulated with the SiO2 NPs/PCT suspension without SiO2 NPs and with 0.5 wt % SiO2 NPs as well as by adjusting different coating layer thicknesses. The surface morphology and chemical compositions of the obtained coating materials were analyzed by field emission scanning electron microscopy with energy-dispersive X-ray spectroscopy and X-ray photoelectron spectroscopy. The transparency and static contact angle of coated samples were measured by UV-visible spectrophotometry and drop shape analysis, respectively. It was concluded that our novel hybrid coating materials exhibited excellent antibacterial and antifogging properties with extremely high scratch resistance and transparency.

Background: Activating transcription factor 3 (ATF3) plays a significant role in cancer development and progression. We investigated the association between variants in expression quantitative trait loci (eQTLs) within ATF3 binding regions and the prognosis of non-small cell lung cancer (NSCLC) after surgery. Methods: A total of 772 patients with NSCLC who underwent curative surgery were enrolled. Using a public database (http://galaxyproject.org), we selected 104 single nucleotide polymorphisms (SNPs) in eQTLs in the ATF3 binding regions. The association of those SNPs with disease-free survival (DFS) was evaluated. Results: Among those SNPs, HAX1 rs11265425T>G was associated with significantly worse DFS (aHR = 1.30, 95% CI = 1.00–1.69, p = 0.05), and ME3 rs10400291C>A was associated with significantly better DFS (aHR = 0.66, 95% CI = 0.46–0.95, p = 0.03). Regarding HAX1 rs11265425T>G, the significant association remained only in adenocarcinoma, and the association was significant only in squamous cell carcinoma regarding ME3 rs10400291C>A. ChIP-qPCR assays showed that the two variants reside in active enhancers where H3K27Ac and ATF3 binding occurs. Promoter assays showed that rs11265425 G allele had significantly higher HAX1 promoter activity than T allele. HAX1 RNA expression was significantly higher in tumor than in normal lung, and higher in rs11265425 TG+GG genotypes than in TT genotype. Conversely, ME3 expression was significantly lower in tumor than in normal lung, and higher in rs10400291 AA genotype than in CC+CA genotypes. Conclusions: In conclusion, this study shows that the functional polymorphisms in ATF3 binding sites, HAX1 rs11265425T>G and ME3 rs10400291C>A are associated with the clinical outcomes of patients in surgically resected NSCLC.

A rapid method for obtaining group B streptococcus (GBS) screening results has been required in the obstetric field. We aimed to determine the diagnostic performance of the Loop-Mediated Isothermal Amplification (LAMP) assay is acceptable compared to the existing polymerase chain reaction (PCR) assay. The study involved 527 pregnant women aged 19 to 44 years. Rectovaginal swabs were collected between 35 and 37 weeks of gestation or prior to impending preterm births or term labor without GBS screening. We presented the diagnostic performance of the LAMP assay with a 95% confidence interval (CI) compared to the PCR and microbiological culture. In total, 115 (21.8%), 115 (21.8%) and 23 (4.4%) patients showed positive results using the LAMP, PCR assay and microbiological culture method, respectively. The LAMP assay showed 100% sensitivity (95% CI, 96.8–100.0), 100% specificity (95% CI, 99.1–100.0) and 100% diagnostic accuracy (95% CI, 99.3–100.0) with the reference being the PCR assay. Meanwhile, the LAMP assay showed 87.0% sensitivity (95% CI, 71.0–100.0), 81.2% specificity (95% CI, 77.6–84.7), and 81.4% diagnostic accuracy (95% CI, 78.0–84.8) with the microbiological culture as a reference. This study presented the LAMP assay as an acceptable method for GBS screening with a similar performance to the existing PCR method.

Background/AimsTo analyse the long-term anatomic and visual outcomes of patients with peripapillary pachychoroid syndrome (PPS), a recently described entity in the pachychoroid disease spectrum.MethodsThis study retrospectively included patients from several retina centres worldwide. Visual acuity (VA), retinal thickness and choroidal thickness at baseline, 6 months and final follow-up were assessed. Temporal trends in VA and anatomic characteristics were evaluated. Visual and anatomic outcomes in eyes that were observed versus those that were treated were analysed.ResultsFifty-six eyes of 35 patients were included with mean follow-up of 27±17 months. Median VA was 20/36 at baseline and remained stable through follow-up (p=0.77). Retinal thickness significantly decreased subfoveally (p=0.012), 1.5 mm nasal to the fovea (p=0.002) and 3.0 mm nasal to the fovea (p=0.0035) corresponding to areas of increased thickening at baseline. Choroidal thickness significantly decreased subfoveally (p=0.0030) and 1.5 mm nasal to the fovea (p=0.0030). Forty-three eyes were treated with modalities including antivascular endothelial growth factor injection, photodynamic therapy, and others. VA remained stable in treated eyes over follow-up (p=0.67). An isolated peripapillary fluid pocket in the outer nuclear layer was characteristic of PPS.ConclusionPatients with PPS experienced decreased retinal oedema and decreased choroidal thickening throughout the course of disease. While some patients experienced visual decline, the overall visual outcome was relatively favourable and independent of trends in retinal or choroidal thickening.

A series of novel structured latex particles with semi-interpenetrating polymer network (IPN) of glassy styrene-acrylonitrile copolymer (SAN) cores and rubbery polyurethane (PU) shells were synthes...

Since a production line for 3D printing is easier to change a product model than that for traditional manufacturing one, 3D printing technology is developing and growing faster than most other tech...

In this study, we synthesized non-isocyanate poly(hydroxyurethane)s (NI-PHUs) via the polyaddition of bis(cyclic carbonate)s and diamines. Bis(cyclic carbonate)s were prepared by reacting resorcino...

Recently, conventional solvent-typed polyurethanes are subject to many regulations due to emission of organic volatile compounds(VOCs) and researches have been focused on eco-friendly waterborne po...

The degradability of degradable polymers is the most important property to determine the lifetime of commercial applications. To control degradation rate and thermal properties, enantiomeric block ...

Although a photo curing is more efficient in terms of time, solvent, and cost than a thermal one, photo-curable coatings require low viscosity and fast curing speed due to workability and time savi...

Over the past few years, silicone-based polymers have been widely studied because silicone shows unique surface properties, such as hydrophobicity, film formability, etc and then silicone-based com...

We designed and synthesized two novel low band gap small molecule donors (M1 and M2) that consist of benzo[1,2-b:4,5-b′]dithiophene as the electron-rich core and 6,7-difluoroquinoxaline as the elec...

Synthesis of zeolitic materials with coal fly ash (CFA) using a fusion/hydrothermal method was performed by various crystallization parameters such as aging time, crystallization time, crystallizat...

UV-curable coatings have numerous advantages, including environmental sustainability due to 100% solid content, economic feasibility attributable to relatively fast curing time, decent appearance, mechanical properties, chemical resistance, and abrasion resistance. However, UV-curable polyurethane acrylate coatings on metals apparently restrict their engineering applications owing to low mechanical properties and poor thermal stability, giving UV-curable coatings less flexibility and formability. In this study, we evaluated the property change of films according to the type of reactive diluents that lowers the viscosity of UV-curing coatings for pre-coated metal and has a substantial effect on the curing rate, viscoelastic properties, adhesive properties, and flexibility of the film. Moreover, there are many changes in the properties of coatings according to varied curing conditions in order to evaluate the oxygen inhibition phenomenon during the curing process in the atmosphere. In particular, to evaluate the effect of reactive diluents on forming formability, which is the most crucial property for the pre-coated metal, this study used conventional formability tests, such as t-bending or the Erichsen test. Moreover, a cross-die cup drawing mold with a similar form as failure and Safety Zone was utilized in order to obtain clearer information on its actual formability. The analysis on the effect of failure and safety zone on the material used in press forming was conducted by assessing limit punch height and forming a limit diagram of the manufactured film according to varied reactive diluents.

Several studies have shown that zinc has a significant influence on erectile function. However, no studies evaluating the cellular distribution of free zinc in penile erectile tissue have been performed. Therefore, this study aimed to test whether free zinc is present in penile tissue and whether it may be involved in the electrical stimulation (ES)-induced penile erection.The subjects for this study were 26 young (8-week-old) male C57BL/6J mice. After the cavernous nerve was exposed through a midline stomach incision, 14 mice received ES of the cavernous nerve (ES group), whereas 12 mice did not (control group). Intracavernous pressure (ICP) (consisting of 10 V at a duration of 1 min, frequency of 12 Hz and a pulse width of 1 m/s) was recorded during ES. Immediately after ICP was recorded, penile tissues were harvested for histological and biochemical analysis, including analysis of zinc transporter 3 (ZnT3) and intracellular free zinc levels.The expression of neuronal nitric oxide synthase (nNOS) and endothelial NOS (eNOS) in penile tissue was significantly greater in the ES group than in the control group (p=0.036 and 0.016, respectively). And then, ZnT3 and intracellular free zinc were present in the penile tissue of both groups. However, ZnT3 immunofluorescence in the ES group was more intense in the dorsal nerve bundle (22% increase, p=0.032). The ES group also showed higher intensity N-(6-methoxy-8-quinolyl)-para-toluenesulfonamide (TSQ) fluorescence signals indicative of intracellular free zinc level in the penile tissue compared to the control group (49% increase in dorsal nerve bundle, p=0.001; 50% increase in corpus cavernosum, p=0.001).The results of the study supported the expression and distribution of free zinc in penile tissue and increased levels after penile erection. Therefore, this study provides anatomical evidence for the potential role of free zinc in penile erection.