Integrated proteomics reveals autophagy landscape and an autophagy receptor controlling PKA-RI complex homeostasis in neurons.

Autophagy is a conserved, catabolic process essential for maintaining cellular homeostasis. Malfunctional autophagy contributes to neurodevelopmental and neurodegenerative diseases. However, the exact role and targets of autophagy in human neurons remain elusive. Here we report a systematic investigation of neuronal autophagy targets through integrated proteomics. Deep proteomic profiling of multiple autophagy-deficient lines of human induced neurons, mouse brains, and brain LC3-interactome reveals roles of neuronal autophagy in targeting proteins of multiple cellular organelles/pathways, including endoplasmic reticulum (ER), mitochondria, endosome, Golgi apparatus, synaptic vesicle (SV) for degradation. By combining phosphoproteomics and functional analysis in human and mouse neurons, we uncovered a function of neuronal autophagy in controlling cAMP-PKA and c-FOS-mediated neuronal activity through selective degradation of the protein kinase A - cAMP-binding regulatory (R)-subunit I (PKA-RI) complex. Lack of AKAP11 causes accumulation of the PKA-RI complex in the soma and neurites, demonstrating a constant clearance of PKA-RI complex through AKAP11-mediated degradation in neurons. Our study thus reveals the landscape of autophagy degradation in human neurons and identifies a physiological function of autophagy in controlling homeostasis of PKA-RI complex and specific PKA activity in neurons.

Dweck's Social-Cognitive Model of Achievement Motivation in Science.

Dweck's social-cognitive model has long been used as a basis for achievement motivation research. However, few studies have examined the comprehensive model with interactions between perceived ability and achievement goals, and even fewer studies have focused on this model in a science academic context. With a sample of undergraduates (n = 1,036), the relations among mindsets, science academic self-efficacy, achievement goals, and achievement-related outcomes in science were examined. Fixed mindset related to performance goals. Growth mindset related to mastery goals and the number of courses completed. There was a significant indirect effect of growth mindset on interest value via mastery goals. Contrary to Dweck's model, the relation of performance goals to outcomes did not vary as a function of science academic self-efficacy. The findings provide empirical evidence for a more nuanced understanding of Dweck's model. They provide practical insights for how to support undergraduate students who are pursuing science-related career.

CT Findings of Azygos Venous System: Congenital Variants and Acquired Structural Changes.

The azygos venous system is a crucial conduit of the posterior thorax and potentially vital collateral pathway. However, it is often overlooked clinically and radiologically. This pictorial essay reviews the normal azygos venous anatomy and CT findings of congenital variations and structural changes associated with acquired pathologies.

Patterns, predictors, and outcomes of situated expectancy-value profiles in an introductory chemistry course.

Using latent profile analysis, we identified profiles of expectancy beliefs, perceived values, and perceived costs among 1433 first- and second-year undergraduates in an introductory chemistry course for STEMM majors. We also investigated demographic differences in profile membership and the relation of profiles to chemistry final exam achievement, science/STEMM credits completed, and graduating with a science/STEMM major. Four motivational profiles were identified: Moderately Confident and Costly (profile 1), Mixed Values-Costs/Moderate-High Confidence (profile 2), High Confidence and Values/Moderate-Low Costs (profile 3), and High All (profile 4). Underrepresented students in STEMM were more likely to be in profile 2 relative to profile 3. First-generation college students were more likely to be in profile 4 than profile 3. Finally, students likely to be in profile 3 had higher final exam grades than the other profiles and were more likely to graduate with a science major compared to profile 1. There were no differences in graduating science major between profile 3 and the other two profiles. Thus, profile 3 was most adaptive for both proximal (final exam) and distal (graduating with a science major) outcomes. Results suggest that supporting motivation early in college is important for persistence and ultimately the talent development of undergraduate STEMM students.

Generative Adversarial Network-Based Image Conversion Among Different Computed Tomography Protocols and Vendors: Effects on Accuracy and Variability in Quantifying Regional Disease Patterns of Interstitial Lung Disease.

OBJECTIVE: To assess whether computed tomography (CT) conversion across different scan parameters and manufacturers using a routable generative adversarial network (RouteGAN) can improve the accuracy and variability in quantifying interstitial lung disease (ILD) using a deep learning-based automated software. MATERIALS AND METHODS: This study included patients with ILD who underwent thin-section CT. Unmatched CT images obtained using scanners from four manufacturers (vendors A-D), standard- or low-radiation doses, and sharp or medium kernels were classified into groups 1-7 according to acquisition conditions. CT images in groups 2-7 were converted into the target CT style (Group 1: vendor A, standard dose, and sharp kernel) using a RouteGAN. ILD was quantified on original and converted CT images using a deep learning-based software (Aview, Coreline Soft). The accuracy of quantification was analyzed using the dice similarity coefficient (DSC) and pixel-wise overlap accuracy metrics against manual quantification by a radiologist. Five radiologists evaluated quantification accuracy using a 10-point visual scoring system. RESULTS: Three hundred and fifty CT slices from 150 patients (mean age: 67.6 ± 10.7 years; 56 females) were included. The overlap accuracies for quantifying total abnormalities in groups 2-7 improved after CT conversion (original vs. converted: 0.63 vs. 0.68 for DSC, 0.66 vs. 0.70 for pixel-wise recall, and 0.68 vs. 0.73 for pixel-wise precision; P < 0.002 for all). The DSCs of fibrosis score, honeycombing, and reticulation significantly increased after CT conversion (0.32 vs. 0.64, 0.19 vs. 0.47, and 0.23 vs. 0.54, P < 0.002 for all), whereas those of ground-glass opacity, consolidation, and emphysema did not change significantly or decreased slightly. The radiologists' scores were significantly higher (P < 0.001) and less variable on converted CT. CONCLUSION: CT conversion using a RouteGAN can improve the accuracy and variability of CT images obtained using different scan parameters and manufacturers in deep learning-based quantification of ILD.

Clinical characteristics of rheumatoid arthritis patients with interstitial lung disease: baseline data of a single-center prospective cohort.

BACKGROUND: To introduce a prospective cohort for rheumatoid arthritis (RA) patients with interstitial lung disease (ILD) and to identify their clinical features in comparison with RA patients without ILD. METHODS: Using a multidisciplinary collaborative approach, a single-center cohort for RA patients with ILD (RA-ILD) was established in May 2017, and enrolment data from May 2017 to March 2021 were used to compare the clinical features of RA patients without ILD (RA-non ILD). Multivariable logistic regression analysis was used to identify factors associated with ILD in RA patients. RESULTS: Among 148 RA-ILD and 410 RA-non ILD patients, participants in the RA-ILD group were older (65.8 ± 9.9 vs. 58.0 ± 10.4 years, P < 0.001) and included more males (35.8% vs. 14.6%, P < 0.001) than in the RA-non ILD group. The RA-ILD group had a higher proportion of late-onset RA patients (age ≥ 60 years) than in the comparator group (43.9% vs. 14.2%, P < 0.001). Multivariable logistic regression analysis showed that higher age at RA onset (OR 1.056, 95% CI 1.021-1.091), higher body mass index (BMI; OR 1.65, 95% CI 1.036-2.629), smoking history (OR 2.484, 95% CI 1.071-5.764), and oral glucocorticoid use (OR 3.562, 95% CI 2.160-5.874) were associated with ILD in RA patients, whereas methotrexate use was less likely to be associated with ILD (OR 0.253, 95% CI 0.155-0.412). CONCLUSIONS: Higher age at RA onset, smoking history, and higher BMI were associated with the presence of ILD among RA patients. Oral glucocorticoids were more frequently used whereas methotrexate was less likely to be used in RA-ILD patients.

Development of new tools to study membrane-anchored mammalian Atg8 proteins.

ABBREVIATIONS: A:C autophagic membrane:cytosol; ALS amyotrophic lateral sclerosis; ATG4 autophagy related 4; Atg8 autophagy related 8; BafA1 bafilomycin A1; BNIP3L/Nix BCL2 interacting protein 3 like; CALCOCO2/NDP52 calcium binding and coiled-coil domain 2; EBSS Earle's balanced salt solution; GABARAP GABA type A receptor-associated protein; GST glutathione S transferase; HKO hexa knockout; Kd dissociation constant; LIR LC3-interacting region; MAP1LC3/LC3 microtubule associated protein 1 light chain 3; NLS nuclear localization signal/sequence; PE phosphatidylethanolamine; SpHfl1 Schizosaccharomyces pombeorganic solute transmembrane transporter; SQSTM1/p62 SQSTM1/p62; TARDBP/TDP-43 TAR DNA binding protein; TKO triple knockout.

MUC5B promoter variant rs35705950, rare but significant susceptibility locus in rheumatoid arthritis-interstitial lung disease with usual interstitial pneumonia in Asian populations.

BACKGROUND: MUC5B variant rs35705950 is the common and most significant risk variant for rheumatoid arthritis-interstitial lung disease (RA-ILD) in Western populations. However, little is known about its significant association with RA-ILD in Asian populations. We here investigate the association of rs35705950 with Korean patients with RA-ILD. METHODS: In this cross-sectional study, we genotyped rs35705950 in 2444 patients with RA. Among them, 683 patients with RA who have chest CT were divided into RA-ILD and RA-noILD. RA-ILD was classified as usual interstitial pneumonia (UIP) and other than UIP. The associations of rs35705950 with RA-ILD and its subtype were analysed using multivariable regression adjusted for age at RA diagnosis. Meta-analysis of a previously reported Japanese dataset and Korean dataset obtained for this study was conducted. RESULTS: The minor allele (T) frequency of rs35705950 was 0.37%, 1.43% and 2.38% in 2444 patients with RA, 105 patients with RA-ILD and 63 patients with UIP, respectively. Genotypic association of rs35705950 with RA-ILD was insignificant (OR 2.49, 95% CI 0.64 to 9.69, p=0.187), but showed significant association with UIP (OR 4.90, 95% CI 1.23 to 19.59, p=0.024) compared with RA-noILD. In meta-analysis (123 UIP and 878 RA-noILD) combining our data with previously reported Japanese data, this variant was found to be significantly associated with UIP (OR 3.51, 95% CI 1.19 to 10.37, p=0.023). CONCLUSION: MUC5B variant rs35705950 is a rare but significant risk factor for Asian patients with RA-ILD with UIP, suggesting a sharing of the genetic background between Asian and Western populations.

Regulation of α-synuclein homeostasis and inflammasome activation by microglial autophagy.

Autophagy clears protein aggregates, damaged cellular organelles, and pathogens through the lysosome. Although autophagy is highly conserved across all cell types, its activity in each cell is specifically adapted to carry out distinct physiological functions. The role of autophagy in neurons has been well characterized; however, in glial cells, its function remains largely unknown. Microglia are brain-resident macrophages that survey the brain to remove injured neurons, excessive synapses, protein aggregates, and infectious agents. Current studies have demonstrated that dysfunctional microglia contribute to neurodegenerative diseases. In Alzheimer's disease animal models, microglia play a critical role in regulating amyloid plaque formation and neurotoxicity. However, how microglia are involved in Parkinson's disease (PD) remains poorly understood. Propagation of aggregated α-synuclein via cell-to-cell transmission and neuroinflammation have emerged as important mechanisms underlying neuropathologies in PD. Here, we review converging evidence that microglial autophagy maintains α-synuclein homeostasis, regulates neuroinflammation, and confers neuroprotection in PD experimental models.

A real-world study assessing the impact of retinal fluid on visual acuity outcomes in patients with neovascular age-related macular degeneration in Korea.

To evaluate the real-world treatment outcomes in patients with neovascular age-related macular degeneration (nAMD) in Korea, focusing on retinal fluid resolution. This multi-institutional retrospective chart review study, analyzed medical records of patients with nAMD (age ≥ 50 years) who received their first anti-vascular endothelial growth factor (VEGF) treatment in ophthalmology clinics across South Korea between January 2017 and March 2019. The primary endpoint was the proportion of patients with retinal fluid after 12 months of anti-VEGF treatment. The association between fluid-free period and VA gains was also evaluated. A total of 600 patients were enrolled. At baseline, 97.16% of patients had retinal fluid; after 12 months of anti-VEGF treatment, 58.10% of patients had persistent retinal fluid. VA improvements were relatively better in patients with absence of retinal fluid compared with presence of retinal fluid (+ 12.29 letters vs. + 6.45 letters at month 12; P < .0001). Longer duration of absence of retinal fluid over first 12 months correlated with better VA gains at month 12 (P < .01). More than half of the study patients with nAMD had retinal fluid even after 12 months of treatment with their current anti-VEGF. Presence of retinal fluid was associated with relatively worse VA outcomes.

AKT, a Key Transmitter of HIF-1α and AR Signaling Pathways, Has a Critical Role in the Apigetrin-Mediated Anti-Cancer Effects in Prostate Cancer Cells.

Apigetrin is a flavonoid glycoside phytochemical that is derived from various herbs and exhibits several beneficial biological activities, including anti-oxidant, anti-inflammatory, anti-obesity, and anti-cancer effects. In the present study, we elucidated the anti-cancer effect and targeting mechanism of apigetrin in LNCaP and PC-3 cells through various experiments, including cell viability by CELLOMAXTM Viability Assay kit, cell migration by scratch wound assays, and 2D-and 3D- cell growth assay. Apigetrin inhibited the viability, migration, proliferation, and growth of cells in long-term 2D- and 3D- cultures cell growth. A high dose of apigetrin induced apoptosis, as evidenced by increased cleavage of poly ADP-ribose polymerase (PARP) and caspase-3 (c-cas3) in both LNCaP and PC-3 cells. Furthermore, apigetrin inhibited AR, PSA, HIF-1α, and VEGF expression in LNCaP and PC-3 cells. Apigetrin also suppressed the hypoxia-induced HIF-1α expression in these cells. Furthermore, apigetrin reduced hypoxia-induced VEGF secretion in the culture medium and inhibited hypoxia-induced tube formation of HUVECs. Silencing of AKT revealed that the anti-cancer activity of apigetrin is mediated via AKT. Thus, our data suggest that apigetrin exerts anti-cancer effects by inhibiting AKT, a central key of HIF-1α and AR signaling, in early-and late-stage prostate cancer cells.

Co-Development of Adolescents' Cooperative and Competitive Attitudes: How it Predicts Mental Health and Academic Achievement.

This study used nationally representative longitudinal data in South Korea to examine how joint changes in adolescents' (N = 7324; Mage ≈ 11 years) cooperative and competitive attitudes from sixth to ninth grade relate to mental health and achievement in 10th grade. The parallel process model showed that both cooperative and competitive attitudes declined over time. Higher cooperative attitudes at baseline indicated higher competitive attitudes, and a faster decline in cooperative attitudes indicated a faster decline in competitive attitudes. The intercept of cooperative attitudes was positively related to mental health but negatively related to achievement. Opposite patterns were found for the intercept of competitive attitudes. These findings highlight the usefulness of considering the co-development of cooperative and competitive attitudes.

Cooperative and Competitive Attitudes During Adolescence and Their Social and Academic Outcomes.

Individuals develop diverse social attitudes during adolescence. This study focused on adolescents' cooperative and competitive attitudes from grades 7-11 and their outcomes in grade 12. The sample included 6,908 South Korean adolescents (47.6% girls, mean age = 12.83, range = 12-15). Latent cross-lagged models revealed negative directional associations between cooperative and compet itive attitudes for grades 7-10, but no significant associations for grades 10-11. Cooperative attitudes contributed more to social than academic outcomes, whereas competitive attitudes more positively predicted academic outcomes. The results suggest that educators who support early to mid-adolescents' cooperative or competitive attitudes need to strike a delicate balance as these attitudes do not change independently and both have distinct strengths and weaknesses.

Mediastinal Lymphadenopathy in the National Lung Screening Trial (NLST) Is Associated with Interval Lung Cancer.

Background There are currently no evidence-based guidelines for the management of enlarged mediastinal lymph nodes found on lung cancer screening (LCS) CT scans. Purpose To assess the frequency and clinical significance of enlarged mediastinal lymph nodes on the initial LCS CT scans in National Lung Screening Trial (NLST) participants. Materials and Methods A retrospective review of the NLST database identified all CT trial participants with at least one enlarged (≥1.0 cm) mediastinal lymph node identified by site readers on initial CT scans. Each study was reviewed independently by two thoracic radiologists to measure the two largest nodes and to record morphologic characteristics. Scans with extensively calcified mediastinal lymph nodes or nodes measuring less than 1 cm were excluded. Frequency and time to lung cancer diagnosis, lung cancer stage, and histologic findings were compared between NLST participants with and without lymphadenopathy. Results Of the 26 722 NLST participants, 422 (1.6%) had enlarged noncalcified mediastinal lymph nodes on the initial LCS CT scan. Mediastinal lymphadenopathy was associated with an increase in lung cancer cases (72 of 422 participants [17.1%; 95% CI: 13.6, 21.0] vs 1017 of 26 300 [3.9%; 95% CI: 3.6, 4.1]; P < .001), earlier diagnosis (restricted mean survival time ± standard error, 2285 days ± 44 vs 2611 days ± 2; P < .001), the presence of lung nodules (P < .001), advanced stage at presentation (22 of 72 participants [31%] with cancer at stage IIIA vs 410 of 1017 [40.3%] at stage IA; P < .001), and increased mortality (P < .001). The majority of participants with lung cancers in the LCS group with mediastinal lymphadenopathy were detected at initial LCS CT (50 of 422 participants [11.8%; 95% CI: 8.9, 15.3] vs T1-T7, 22 of 422 [5.3%; 95% CI: 3.3, 7.8]; P < .001). There was no association between mediastinal lymphadenopathy and lung cancer histologic findings, CT appearance, or location of lung nodules (P > .05 based on unadjusted pairwise association analyses). Conclusion Noncalcified mediastinal lymphadenopathy in the low-dose lung cancer screening study sample was associated with an increase in lung cancer, an earlier diagnosis, more advanced-stage disease, and increased mortality. More aggressive treatment of these patients appears warranted. © RSNA, 2021 Online supplemental material is available for this article. See also the editorials by McLoud and by Mascalchi and Zompatori in this issue.

Lactiplantibacillusplantarum ATG-K2 Exerts an Anti-Obesity Effect in High-Fat Diet-Induced Obese Mice by Modulating the Gut Microbiome.

Obesity is a major health problem. Compelling evidence supports the beneficial effects of probiotics on obesity. However, the anti-obesity effect of probiotics remains unknown. In this study, we investigated the anti-obesity effects and potential mechanisms of Lactiplantibacillus plantarum ATG-K2 using 3T3-L1 adipocytes and high-fat diet (HFD)-induced obese mice. 3T3-L1 cells were incubated to determine the effect of lipid accumulation with lysate of L. plantarum ATG-K2. Mice were fed a normal fat diet or HFD with L. plantarum ATG-K2 and Orlistat for 8 weeks. L. plantarum ATG-K2 inhibited lipid accumulation in 3T3-L1 adipocytes, and reduced body weight gain, WAT weight, and adipocyte size in HFD-induced obese mice, concurrently with the downregulation of PPARγ, SREBP1c, and FAS and upregulation of PPARα, CTP1, UCP1, Prdm16, and ND5. Moreover, L. plantarum ATG-K2 decreased TG, T-CHO, leptin, and TNF-α levels in the serum, with corresponding gene expression levels in the intestine. L. plantarum ATG-K2 modulated the gut microbiome by increasing the abundance of the Lactobacillaceae family, which increased SCFA levels and branched SCFAs in the feces. L. plantarum ATG-K2 exhibited an anti-obesity effect and anti-hyperlipidemic effect in 3T3-L1 adipocytes and HFD-induced obese mice by alleviating the inflammatory response and regulating lipid metabolism, which may be influenced by modulation of the gut microbiome and its metabolites. Therefore, L. plantarum ATG-K2 can be a preventive and therapeutic agent for obesity.

Dysfunction of NMDA receptors in neuronal models of an autism spectrum disorder patient with a DSCAM mutation and in Dscam-knockout mice.

Heterogeneity in the etiopathology of autism spectrum disorders (ASD) limits the development of generic remedies, requires individualistic and patient-specific research. Recent progress in human-induced pluripotent stem cell (iPSC) technology provides a novel platform for modeling ASDs for studying complex neuronal phenotypes. In this study, we generated telencephalic induced neuronal (iN) cells from iPSCs derived from an ASD patient with a heterozygous point mutation in the DSCAM gene. The mRNA of DSCAM and the density of DSCAM in dendrites were significantly decreased in ASD compared to control iN cells. RNA sequencing analysis revealed that several synaptic function-related genes including NMDA receptor subunits were downregulated in ASD iN cells. Moreover, NMDA receptor (R)-mediated currents were significantly reduced in ASD compared to control iN cells. Normal NMDA-R-mediated current levels were rescued by expressing wild-type DSCAM in ASD iN cells, and reduced currents were observed by truncated DSCAM expression in control iN cells. shRNA-mediated DSCAM knockdown in control iN cells resulted in the downregulation of an NMDA-R subunit, which was rescued by the overexpression of shRNA-resistant DSCAM. Furthermore, DSCAM was co-localized with NMDA-R components in the dendritic spines of iN cells whereas their co-localizations were significantly reduced in ASD iN cells. Levels of phospho-ERK1/2 were significantly lower in ASD iN cells, suggesting a potential mechanism. A neural stem cell-specific Dscam heterozygous knockout mouse model, showing deficits in social interaction and social memory with reduced NMDA-R currents. These data suggest that DSCAM mutation causes pathological symptoms of ASD by dysregulating NMDA-R function.

Autophagy activity contributes to the impairment of social recognition in Epac2-/- mice.

Autophagy is a lysosomal degradation pathway that regulates cellular homeostasis. It is constitutively active in neurons and controls the essential steps of neuronal development, leading to its dysfunction in neurodevelopmental disorders. Although mTOR-associated impaired autophagy has previously been reported in neurodevelopmental disorders, there is lack of information about the dysregulation of mTOR-independent autophagy in neurodevelopmental disorders. In this study, we investigated whether the loss of Epac2, involved in the mTOR-independent pathway, affects autophagy activity and whether the activity of autophagy is associated with social-behavioral phenotypes in mice with Epac2 deficiencies. We observed an accumulation of autophagosomes and a significant increase in autophagic flux in Epac2-deficient neurons, which had no effect on mTOR activity. Next, we examined whether an increase in autophagic activity contributed to the social behavior exhibited in Epac2-/- mice. The social recognition deficit observed in Epac2-/- mice recovered in double transgenic Epac2-/-: Atg5+/- mice. Our study suggests that excessive autophagy due to Epac2 deficiencies may contribute to social recognition defects through an mTOR-independent pathway.

Lactobacillus plantarum HAC01 ameliorates type 2 diabetes in high-fat diet and streptozotocin-induced diabetic mice in association with modulating the gut microbiota.

Type 2 diabetes mellitus (T2DM) is a serious metabolic disorder that occurs worldwide; however, this condition can be managed with probiotics. We assessed the potential therapeutic effects of Lactobacillus plantarum HAC01 on hyperglycemia and T2DM and determined their potential mechanisms using mice with high-fat diet (HFD) and streptozotocin (STZ)-induced diabetes. The diabetic model was established with an HFD and 50 mg kg-1 STZ. L. plantarum HAC01 was then administered for 10 weeks. Body weight, food and water intake, biochemical parameters, and homeostasis model assessment for insulin resistance (HOMA-IR) were measured. Oral glucose tolerance test and histological analysis were performed, and the glucose metabolism-related gene expression and signaling pathways in the liver were determined. Fecal microbiota and serum short-chain fatty acids (SCFAs) were also analyzed. L. plantarum HAC01 significantly lowered blood glucose and HbA1c levels and improved glucose tolerance and HOMA-IR. Additionally, it increased the insulin-positive ß-cell area in islets and decreased the mRNA expression levels of phosphoenolpyruvate carboxykinase and glucose 6-phosphatase, which are associated with gluconeogenesis. L. plantarum HAC01 also increased the phosphorylation of AMPK and Akt, which are involved in glucose metabolism in the liver. Notably, L. plantarum HAC01 increased the Akkermansiaceae family and increased SCFAs in serum. L. plantarum HAC01 could alleviate hyperglycemia and T2DM by regulating glucose metabolism in the liver, protecting the islet ß-cell mass, and restoring the gut microbiota and SCFAs. L. plantarum HAC01 may thus be an effective therapeutic agent for T2DM.

Real-World Effectiveness, Treatment Pattern, and Safety of Ranibizumab in Korean Patients with Neovascular Age-Related Macular Degeneration: Subgroup Analyses from the LUMINOUS Study.

PURPOSE: To evaluate the real-world effectiveness, treatment patterns, and safety of ranibizumab in Korean patients with neovascular age-related macular degeneration (nAMD). METHODS: LUMINOUS™ is a 5-year, global, prospective, observational, open-label study. Adults aged ≥18 years who were either treatment-naïve or prior-treated were enrolled and treated with ranibizumab 0.5 mg as per the local label. Outcome measures included mean (± standard deviation [SD]) changes from baseline in visual acuity (VA) and central retinal thickness (CRT), and rate of ocular and non-ocular adverse events (AEs). RESULTS: Overall, 367 Korean patients with nAMD (152 treatment-naïve and 215 prior-treated) were enrolled. The mean (SD) VA changes from baseline at 1-year were +10.1 (±21.77; P=0.0005) and +1.4 (±15.17; P=0.2142) Early Treatment Diabetic Retinopathy Study letters, with mean numbers of injections of 5.2 and 3.4 in the treatment-naïve and prior-treated groups, respectively. VA gains were greater in patients with lower baseline VA, who received a loading dose, and with polypoidal choroidal vasculopathy (PCV). Multivariate logistic regression analyses demonstrated younger age, worse baseline VA, and those who received loading dose being associated with higher odds of any gain in VA at 1 year (P<0.05). Mean (SD) CRT changes from baseline were -126.7 (±174.90) µm (P<0.0001) and +10.8 (±89.62) µm (P=0.5833) in the treatment-naïve and prior-treated groups, respectively, with greater reductions observed in patients with PCV. Ocular and non-ocular AEs were reported in 8.4% (n=31) and 10.1% (n=37) of patients, respectively. CONCLUSION: The LUMINOUS study confirms real-world effectiveness and safety of ranibizumab in Korean patients with nAMD; factors including age, baseline VA, and loading-dose were associated with VA gain at one-year post-treatment.

Stereotype Threat in High School Classrooms: How It Links to Teacher Mindset Climate, Mathematics Anxiety, and Achievement.

As stereotype threat was initially examined in experimental settings, the effects of such threats have often been tested by temporarily manipulating social identity threats. This study expands the literature by examining 9th-grade adolescents' naturalistic stereotype threat, using data from the National Study of Learning Mindsets in the United States (n ~= 6040, age: 13-17, Mage = 14.31, 6.9% Black boys, 6.5% Black girls, 13.1% Latinos, 12.3% Latinas, 31.5% White boys, 29.7% White girls). The results indicate that Black and Latinx students experience higher levels of stereotype threat in high school mathematics classrooms than do their White peers. When students perceive that their teachers have created fixed mindset climates, they experience greater stereotype threat. Stereotype threat, in turn, negatively predicts Black and Latino boys and White girls' later achievement via anxiety. These findings highlight the importance of creating mathematics classrooms that cultivate a growth mindset and minimize social identity threat.