Case-case genome-wide association analysis identifying genetic loci with divergent effects on Crohn's disease and ulcerative colitis.

Crohn's disease (CD) and ulcerative colitis (UC), two major subtypes of inflammatory bowel disease, show substantial differences in their clinical course and treatment response. To identify the genetic factors underlying the distinct characteristics of these two diseases, we performed a genome-wide association study (GWAS) between CD (n = 2359) and UC (n = 2175) in a Korean population, followed by replication in an independent sample of 772 CD and 619 UC cases. Two novel loci were identified with divergent effects on CD and UC: rs9842650 in CD200 and rs885026 in NCOR2. In addition, the seven established susceptibility loci [major histocompatibility complex (MHC), TNFSF15, OTUD3, USP12, IL23R, FCHSD2 and RIPK2] reached genome-wide significance. Of the nine loci, six (MHC, TNFSF15, OTUD3, USP12, IL23R and CD200) were replicated in the case-case GWAS of European populations. The proportion of variance explained in CD-UC status by polygenic risk score analysis was up to 22.6%. The area under the receiver-operating characteristic curve value was 0.74, suggesting acceptable discrimination between CD and UC. This CD-UC GWAS provides new insights into genetic differences between the two diseases with similar symptoms and might be useful in improving their diagnosis and treatment.

A Prospective Sociocentric Study of 2 Entire Traditional Korean Villages: The Korean Social Life, Health, and Aging Project (KSHAP).

The Korean Social Life, Health, and Aging Project (KSHAP) was a multidisciplinary prospective study conducted in South Korea that measured various health biomarkers from blood, hair, and brain magnetic resonance imaging, and we examined their associations with sociocentric (global) social network data of older adults in 2 entire villages (or cohorts). Cohort K included participants aged 60 years or older, and cohort L included participants aged 65 years or older. We performed a baseline survey involving 814 of the 860 individuals (94.7% response rate) in cohort K in 2012 and 947 of the 1,043 individuals (90.8% response rate) in cohort L in 2017. We gathered longitudinal data for 5 waves in cohort K from 2011 to 2019 and 2 waves in cohort L from 2017 to 2022. Here, we describe for the first time the follow-up design of the KSHAP, the changes in social networks, and various biomarkers over a number of years. The data for cohort K are publicly available via the Korean Social Science Data Archive as well as the project website, and the data for cohort L will be shared soon.

Identification of shared loci associated with both Crohn's disease and leprosy in East Asians.

Genome-wide association studies (GWAS) of Crohn's disease (CD) in European and leprosy in Chinese population have shown that CD and leprosy share genetic risk loci. As these shared loci were identified through cross-comparisons across different ethnic populations, we hypothesized that meta-analysis of GWAS on CD and leprosy in East Asian populations would increase power to identify additional shared loci. We performed a cross-disease meta-analysis of GWAS data from CD (1621 cases and 4419 controls) and leprosy (2901 cases 3801 controls) followed by replication in additional datasets comprising 738 CD cases and 488 controls and 842 leprosy cases and 925 controls. We identified one novel locus at 7p22.3, rs77992257 in intron 2 of ADAP1, shared between CD and leprosy with genome-wide significance (P = 3.80 × 10-11) and confirmed 10 previously established loci in both diseases: IL23R, IL18RAP, IL12B, RIPK2, TNFSF15, ZNF365-EGR2, CCDC88B, LACC1, IL27, NOD2. Phenotype variance explained by the polygenic risk scores derived from Chinese leprosy data explained up to 5.28% of variance of Korean CD, supporting similar genetic structures between the two diseases. Although CD and leprosy shared a substantial number of genetic susceptibility loci in East Asians, the majority of shared susceptibility loci showed allelic effects in the opposite direction. Investigation of the genetic correlation using cross-trait linkage disequilibrium score regression also showed a negative genetic correlation between CD and leprosy (rg [SE] = -0.40[0.13], P = 2.6 × 10-3). These observations implicate the possibility that CD might be caused by hyper-sensitive reactions toward pathogenic stimuli.

Characterization of Th17 tissue-resident memory cells in non-inflamed intestinal tissue of Crohn's disease patients.

Crohn's disease (CD) is a chronic inflammatory disorder affecting the bowel wall. Tissue-resident memory T (Trm) cells are implicated in CD, yet their characteristics remain unclear. We aimed to investigate the transcriptional profiles and functional characteristics of Trm cells in the small bowel of CD and their interactions with immune cells. Seven patients with CD and four with ulcerative colitis as controls were included. Single-cell RNA sequencing and paired T cell receptor sequencing assessed T cell subsets and transcriptional signatures in lamina propria (LP) and submucosa/muscularis propria-enriched fractions (SM/MP) from small bowel tissue samples. We detected 58,123 T cells grouped into 16 populations, including the CD4+ Trm cells with a Th17 signature and CD8+ Trm clusters. In CD, CD4+ Trm cells with a Th17 signature, termed Th17 Trm, showed significantly increased proportions within both the LP and SM/MP areas. The Th17 Trm cluster demonstrated heightened expression of tissue-residency marker genes (ITGAE, ITGA1, and CXCR6) along with elevated levels of IL17A, IL22, CCR6, and CCL20. The clonal expansion of Th17 Trm cells in CD was accompanied by enhanced transmural dynamic potential, as indicated by significantly higher migration scores. CD-prominent Th17 Trm cells displayed an increased interferon gamma (IFNγ)-related signature possibly linked with STAT1 activation, inducing chemokines (i.e., CXCL10, CXCL8, and CXCL9) in myeloid cells. Our findings underscored the elevated Th17 Trm cells throughout the small bowel in CD, contributing to disease pathogenesis through IFNγ induction and subsequent chemokine production in myeloid cells.

Transcutaneous electrical nerve stimulation and catheter-related bladder discomfort following transurethral resection of bladder tumour: A randomised controlled trial.

BACKGROUND: Catheter-related bladder discomfort (CRBD) is problematic in patients with a urinary catheter. Transcutaneous electrical nerve stimulation (TENS) is a non-invasive analgesic modality used to relieve various types of pain. OBJECTIVES: We evaluated the effect of TENS on CRBD after transurethral resection of bladder tumours (TURBT). DESIGN: A randomised controlled trial. SETTING: A large university tertiary hospital, from October 2022 to March 2023. PATIENTS: Patients requiring urinary catheterisation after TURBT. INTERVENTION: In this randomised controlled trial, patients were randomly allocated to the TENS (n  = 56) or control (n  = 56) groups. CRBD manifests as a burning sensation with an urge to void or discomfort in the suprapubic area. Moderate to severe CRBD was defined as patients self-reporting CRBD symptoms with or without behavioural response, including attempts to remove the urinary catheter, intense verbal reactions, and flailing limbs. TENS was performed from the end of surgery to 1 h postoperatively. MAIN OUTCOME MEASURE: The primary endpoint was considered moderate to severe CRBD immediately postoperatively. Secondary endpoints included moderate to severe CRBD at 1, 2 and 6 h postoperatively. Additionally, postoperative pain, patient satisfaction, and TENS-related adverse effects were evaluated. RESULTS: Moderate to severe CRBD immediately postoperatively was significantly less frequent in the TENS group than in the control group: 10 (17.9%) vs. 34 (60.7%); P < 0.001; relative risk (95% CI) = 0.294 (0.161 to 0.536); absolute risk reduction = 0.43; number needed to treat = 2.3. Moderate to severe CRBD differed between the two groups at 1 h postoperatively: 1 (1.8%) vs. 16 (28.6%); P < 0.001; relative risk = 0.06 (95% CI 0.01 to 0.46); absolute risk reduction = 0.27; number needed to treat = 3.7. The TENS group exhibited a significantly lower score for postoperative pain at 1 h (1.8 ±â€Š0.6 vs. 2.2 ±â€Š0.4; P < 0.001, mean difference (95% CI) = 0.4 (0.2 to 0.6) and a higher score for patient satisfaction, 5.0 (4.0 to 6.0) vs. 3.0 (3.0 to 4.0); P < 0.001; median difference (95% CI) = 2.0 (1.0 to 2.0). CONCLUSIONS: TENS reduced moderate to severe CRBD, decreased postoperative pain, and increased patient satisfaction after TURBT. CLINICAL TRIAL REGISTRY: Clinical Research Information Service (KCT0007450). VISUAL ABSTRACT: http://links.lww.com/EJA/B12.

The Inhibitory Effects of Maclurin on Fatty Acid Synthase and Adipocyte Differentiation.

Obesity is a complex health condition characterized by excessive adipose tissue accumulation, leading to significant metabolic disturbances such as insulin resistance and cardiovascular diseases. Fatty acid synthase (FAS), a key enzyme in lipogenesis, has been identified as a potential therapeutic target for obesity due to its role in adipocyte differentiation and lipid accumulation. This study employed a multidisciplinary approach involving in silico and in vitro analyses to investigate the anti-adipogenic properties of maclurin, a natural phenolic compound derived from Morus alba. Using SwissDock software (ChEMBL version 23), we predicted protein interactions and demonstrated a high probability (95.6%) of maclurin targeting FAS, surpassing the interaction rates of established inhibitors like cerulenin. Docking simulations revealed maclurin's superior binding affinity to FAS, with a binding score of -7.3 kcal/mol compared to -6.7 kcal/mol for cerulenin. Subsequent in vitro assays confirmed these findings, with maclurin effectively inhibiting FAS activity in a concentration-dependent manner in 3T3-L1 adipocytes, without compromising cell viability. Furthermore, maclurin treatment resulted in significant reductions in lipid accumulation and the downregulated expression of critical adipogenic genes such as PPARγ, C/EBPα, and FAS, indicating the suppression of adipocyte differentiation. Maclurin shows potential as a novel FAS inhibitor with significant anti-adipogenic effects, offering a promising therapeutic avenue for the treatment and prevention of obesity.

Digital Literacy and Associated Factors in Older Adults Living in Urban South Korea: A Qualitative Study.

This study aimed to explore digital literacy among community-dwelling older adults in urban South Korea. A semistructured interview guide was developed using the Digital Competence ( 2.0 framework, which emphasizes the competencies for full digital participation in five categories: information and data literacy, communication and collaboration, content creation, safety, and problem-solving. The data were analyzed using combined inductive and deductive content analysis. Inductive analysis identified three main categories: perceived ability to use digital technology, responses to digital technology, and contextual factors. In the results of deductive analysis, participants reported varying abilities in using digital technologies for information and data literacy, communication or collaboration, and problem-solving. However, their abilities were limited in handling the safety or security of digital technology and lacked in creating digital content. Responses to digital technology contain subcategories of perception (positive or negative) and behavior (trying or avoidance). Regarding contextual factors, aging-related physical and cognitive changes were identified as barriers to digital literacy. The influence of families or peers was viewed as both a facilitator and a barrier. Our participants recognized the importance of using digital devices to keep up with the trend of digitalization, but their digital literacy was mostly limited to relatively simple levels.

Impact of Chart-Derived Frailty Index on 1-Year Mortality After Radical Cystectomy in 1004 Patients with Bladder Cancer.

BACKGROUND: Radical cystectomy is a major urological procedure with high morbidity and mortality. The chart-derived frailty index (CFI), a measure of preoperative frailty, can be calculated by using demographic and routine laboratory variables. We assessed the impact of CFI on 1-year mortality after radical cystectomy. METHODS: This retrospective study included patients with bladder cancer who underwent radical cystectomy between 2007 and 2021. The CFI was calculated as the sum of the presence of the following parameters: age > 70 years, body mass index < 18.5 kg/m2, hematocrit < 35%, albumin < 3.4 g/dL, and creatinine > 2.0 mg/dL. Patients were divided into those with low (0-2) and high (3-5) CFI. The 1-year, all-cause and cancer-specific mortalities after radical cystectomy were evaluated. RESULTS: Of the 1004 patients, 914 (91.0%) had a low CFI and 90 (9.0%) had a high CFI. The 1-year, all-cause mortality in the low and high CFI groups was 12.0% and 27.8%, respectively (P < 0.001). Multivariate Cox regression analysis revealed that high CFI (P < 0.001), tumor stage (P = 0.003), and red blood cell transfusion amount (P < 0.001) were significantly associated with 1-year, all-cause mortality after radical cystectomy. Kaplan-Meier survival analysis demonstrated significantly different 1-year, all-cause and cancer-specific mortalities after radical cystectomy between patients with a high CFI and those with a low CFI (log-rank test, both P < 0.001). CONCLUSIONS: High CFI is associated with higher 1-year mortality after radical cystectomy, suggesting that the CFI can effectively predict mortality after radical cystectomy.

QUANTITATIVE ANALYSIS OF CHOROIDAL MORPHOLOGY USING MULTIMODAL IMAGING IN ACUTE AND PERSISTENT CENTRAL SEROUS CHORIORETINOPATHY.

PURPOSE: To analyze quantitative differences in choroidal morphology between acute and persistent central serous chorioretinopathy using multimodal images. METHODS: Ultra-widefield indocyanine green angiography (UWICGA) and optical coherence tomography images of 72 eyes of 72 patients with acute (32 eyes) and persistent (40 eyes) central serous chorioretinopathy were collected. Choroidal thickness, area, vessel density, symmetry, and intervortex anastomosis were assessed. RESULTS: The choroidal area on optical coherence tomography B-scan images was smaller and the choroidal vessel density on UWICGA images was lower in the persistent group ( P < 0.001 and P = 0.028, respectively). Choroidal vessel density on UWICGA showed positive correlation with that of vortex ampullae (all P ≤ 0.046). The constitution of the intervortex anastomosis and dominant vessels in the macular area showed differences between the groups ( P = 0.014 and P = 0.010, respectively), with greater inferonasal vessel participation in the anastomosis and combined superotemporal and inferotemporal vessels as dominant vessels in the persistent groups. CONCLUSION: Acute and persistent central serous chorioretinopathy differed in subfoveal choroidal area, choroidal vessel density, and intervortex anastomosis constitution on UWICGA images. Choroidal vessel density on UWICGA images correlated with that of vortex ampullae. These findings enhance our understanding of the pathophysiology of central serous chorioretinopathy subtypes.

Everyday Digital Literacy Questionnaire for Older Adults: Instrument Development and Validation Study.

BACKGROUND: The need for digital literacy in aging populations is increasing in the digitalizing society. Digital literacy involves the identification, evaluation, and communication of information through various digital devices or relevant programs. OBJECTIVE: The aims of this study were to develop an Everyday Digital Literacy Questionnaire (EDLQ), a digital literacy assessment scale, and subsequently evaluate its psychometric properties using a population of community-dwelling older adults in South Korea. METHODS: The EDLQ was developed using an instrument development design. A nationwide survey was conducted, and the study included 1016 community-dwelling older adults (age ≥60 years). To evaluate the psychometric properties, the participants were randomly divided into 2 groups (n=508 each), and the internal consistency (Cronbach α and McDonald ω), structural validity (exploratory factor analysis and confirmatory factor analysis), hypothesis-testing construct validity using the eHealth Literacy Scale (eHEALS), and measurement invariance were analyzed. RESULTS: Among the initial 30 items of the EDLQ, 22 items with a 3-factor solution had a total explained variance of 77%. The domains included "information and communication" (9 items), "content creation and management" (4 items), and "safety and security" (9 items). Confirmatory factor analysis was conducted with this 3-factor solution (χ2206=345.1; normed χ2206=1.7; comparative fit index=0.997; Tucker-Lewis index=0.997; root-mean-square error of approximation=0.036; standardized root-mean-square residual=0.050; composite reliability=0.903-0.959; average variance extracted=0.699-0.724; R2=0.616-0.773). Hypothesis-testing construct validity with the eHEALS revealed a strong correlation (r=0.75). Cronbach α and McDonald ω coefficients were .98 and 0.98, respectively. The fit indices for measurement invariance, including the configural, metric, and scalar invariance models, demonstrated a satisfactory fit to the data. Our findings suggest that the psychometric properties of the 22-item EDLQ are valid and reliable for assessing digital literacy among older Korean adults. CONCLUSIONS: In this study, we developed a digital literacy measure with strong psychometric properties that made it suitable for assessing the digital literacy of community-dwelling older adults in Korea. To broaden its applicability, however, further assessment of its feasibility for use with different languages and cultures is necessary. Moreover, more empirical research on digital literacy and related factors in older adults can facilitate the development of personalized digital health care services and educational interventions in the digital society.

e-Health for Traumatized Refugees: A Scoping Review.

Background: High prevalence of post-traumatic stress disorder (PTSD) is reported among refugees exposed to traumatic experiences, while escaping from their home country, entering a third country, and adjusting to a new society. Electronic health (e-health) treatments have been utilized to overcome challenges such as high costs, limited access to care, and a shortage of resources faced by traumatized refugees. Objective: The aim of this scoping review was to summarize the current science on e-health to screen and treat PTSD in traumatized refugees, examine its benefits and challenges, and suggest strategies for future research. Methods: We conducted a scoping review guided by Arksey and O'Malley's 6-stage scoping review framework. Results: Of the 2,782 articles identified, 8 studies were included for the final analysis. Due to the heterogeneity of studies, the synthesis of results was not feasible. However, the findings of individual studies were examined. The most commonly used technology modality was the smartphone (n = 5). One study revealed the possibility of telephonic screening of PTSD to be equally efficacious as in-person screening, and all interventions through smartphone and the internet reported high feasibility and acceptability. Conclusion: e-Health is suggested to be a novel and scalable platform to provide mental health care in settings with limited resources. Larger and highly robust studies in refugee populations with PTSD-targeted, theory-based approaches and diverse technological formats such as video conferencing and virtual reality are warranted.

Inflammatory cytokines and retinal nonperfusion area in quiescent proliferative diabetic retinopathy.

PURPOSE: We sought to investigate the association between inflammatory cytokine levels and retinal capillary nonperfusion area in eyes with quiescent proliferative diabetic retinopathy (PDR). METHODS: Samples of aqueous humor were collected from 67 eyes (n = 42 patients) with treatment-naïve PDR. Levels of interleukin (IL)-10, IL-1ß, IL-6, IL-8, monocyte chemoattractant protein 1 (MCP-1), and tumor necrosis factor-α (TNF-α) were obtained using multiplex bead assay. Areas of capillary nonperfusion at the posterior pole and peripheral retina were measured via ultra-widefield fluorescein angiography and correlated with cytokine levels. RESULTS: The levels of IL-10, IL-6, IL-8, MCP-1, and TNF-α were positively correlated with the nonperfusion area of the peripheral retina (r = 0.298, 0.401, 0.265, 0.435, and 0.393; all P ≤ 0.030). There were positive correlations between IL and 10, IL-6, IL-8, MCP-1, and TNF-α (all R ≥ 0.247; all P ≤ 0.043). IL-1ß did not show a significant correlation with the nonperfusion area (P = 0.972 for posterior pole and 0.392 for periphery) but was positively correlated with TNF-α (r = 0.334; P = 0.006). CONCLUSIONS: An increased level of inflammation was observed in PDR eyes with larger nonperfusion areas, which suggests inflammation as a possible target for suppressing PDR progression associated with nonperfusion.

Design of Volumetric Nanolayers via Rapid Proteolysis of Silk Fibroin for Tissue Engineering.

Various methods have been studied to make a regenerated silk fibroin solution. However, most of them take too much time and effort to liquefy. Here, we report that a regenerated silk fibroin solution could be prepared within seconds through acid proteolysis for the first time. The solubilized fibroin could be applied to advanced tissue engineering. Our method shortened the production time to one day (more than 10 times) compared to the general fibroin solution preparation method. It was confirmed that the initial protein affinity nearly doubled from 0.028 to 0.076 µg·mm-2 in FF(ac) compared to FF(aq). A fibroin nanofiber layer having a volumetric hierarchical structure was prepared by electrospinning an acid-proteolyzed fibroin solution, followed by gas foaming. In vitro results of cell adhesion and proliferation capacity of the gas-foamed scaffold were not significantly different compared to the two-dimensional (2D) fibroin nanofiber membrane, overcoming the limitations of volumetric nanofiber scaffolds. We are confident that our research will greatly contribute to the development of regenerative engineering using other proteins.

Determinants of adherence to personal preventive behaviours based on the health belief model: a cross-sectional study in South Korea during the initial stage of the COVID-19 pandemic.

BACKGROUND: Along with the rapid transmission of COVID-19, adherence to preventive behaviours plays a crucial role with respect to the control of COVID-19. However, different individuals' psychological characteristics and risk perception result in various forms of response to preventive behaviours. Based on the Health Belief Model, this study identifies the factors associated with preventive behaviours towards COVID-19 in South Korea during the initial stage of the COVID-19 pandemic. METHODS: A cross-sectional study was conducted in April 2020 through an anonymous online survey. A total of 1207 people in the age bracket of 20-59 years participated in the survey. Single and multiple linear regression analyses were conducted to identify the determinants of preventive behaviours against COVID-19. RESULTS: The following factors were associated with preventive behaviours towards COVID-19: female gender (ß = .124, p < 0.001), has a master's degree or above (ß = 0.065, p = 0.010), perceived susceptibility (ß = .197, p < 0.001), self-efficacy (ß = .404, p < 0.001), trust in radio (ß = -.080, p = .006), trust in official government website (ß = .057, p = .045), trust in social networks (ß = .054, p = .033), and trust in family and friends (ß = .068, p = .009), with an explanatory power of 41.5% (R2 = 0.415). CONCLUSIONS: To flatten the epidemic curve, it is important to understand the public's risk perception and the motivation behind behavioural responses that aim to promote preventive behaviours among the public. Thus, this study calls for the provision of accessible and credible information sources and demonstrates a public health campaign that encourages the public's engagement in preventive behaviours towards COVID-19.

Potential Beneficial Effects of Sargassum spp. in Skin Aging.

Seaweeds are receiving much attention as a rich source of bioactive compounds with cosmeceutical potential. Recent studies have revealed that Sargassum spp., a genus of brown algae in the family Sargassaceae, has multiple functions in preventing and improving skin aging. Sargassum spp. contains many bioactive compounds, such as fucoidan, fucoxanthin, terpenoids, flavonoids, and meroterpenoids. These Sargassum spp. extracts and derivative compounds have excellent potential for skincare, as they exhibit skin health-promoting properties, including antioxidants, anti-inflammation, whitening, skin barrier repair, and moisturizing. Therefore, searching for bioactive compounds in marine resources such as Sargassum spp. could be an attractive approach to preventing and improving skin aging. The current review focused on the various biological abilities of Sargassum extracts or derived compounds for anti-skin aging.

Gender differences in the longitudinal association between husbands' and wives' depressive symptoms among Korean older adults: the moderating effects of the spousal relationship.

PURPOSE: The mutual effects of depressive symptoms between couples have long been reported; however, it remains unknown whether the spousal concordance in depressive symptoms differs depending on spousal relationships. METHOD: Data on 291 married couples from the Korean Social Life, Health, and Aging Project (KSHAP) were examined. The KSHAP collected global network data from the target population living in one Korean village over eight years and across five waves. A seemingly unrelated regression (SUR) model in the panel data was employed to address correlations and heterogeneity. RESULTS: If one spouse (husband or wife) had depressive symptoms, the other spouse tended to have depressive symptoms. However, the effect of marital relations on spousal concordance in depressive symptoms was different among husbands and wives. This study demonstrated both spousal support and spousal network aspects of spousal relationships. Depression concordance was stronger for couples with more negative marital relationship. A supportive marital relationship was associated with less concordance between spouses' depressive symptoms for wives but not for husbands. Spousal network overlap was associated with less depression concordance for husbands; however, for wives, spousal network overlap was directly associated with more depressive symptoms and did not mediate the association with depression concordance. CONCLUSION: Our findings suggest that approaches to supporting older adults dealing with mental health disorders may involve support at both the individual and couple levels. Gender-specific strategies could also be devised to improve the mental well-being of the older population.

Classification of pachychoroid on optical coherence tomography using deep learning.

PURPOSE: Pachychoroid is characterized by dilated Haller vessels and choriocapillaris attenuation that are seen on optical coherence tomography (OCT) B-scans. This study investigated the feasibility of using deep learning (DL) models to classify pachychoroid and non-pachychoroid eyes from OCT B-scan images. METHODS: In total, 1898 OCT B-scan images were collected from eyes with macular diseases. Images were labeled as pachychoroid or non-pachychoroid based on strict quantitative and qualitative criteria for multimodal imaging analysis by two retina specialists. DL models were trained (80%) and validated (20%) using pretrained convolutional neural networks (CNNs). Model performance was assessed using an independent test set of 50 non-pachychoroid and 50 pachychoroid images. RESULTS: The final accuracy of AlexNet and VGG-16 was 57.52% for both models. ResNet50, Inception-v3, Inception-ResNet-v2, and Xception showed a final accuracy of 96.31%, 95.25%, 93.40%, and 92.61%, respectively, for the validation set. These models demonstrated accuracy on an independent test set of 78.00%, 86.00%, 90.00%, and 92.00%, and an F1 score of 0.718, 0.841, 0.894, and 0.920, respectively. CONCLUSION: DL models classified pachychoroid and non-pachychoroid images with good performance. Accurate classification can be achieved using CNN models with deep rather than shallow neural networks.

Cytokines associated with hemorrhage in proliferative diabetic retinopathy.

PURPOSE: To investigate aqueous cytokine levels in association with hemorrhage in proliferative diabetic retinopathy (PDR) in patients with type 2 diabetes mellitus. METHODS: Sixty-six eyes with treatment-naïve PDR, including 26 hemorrhagic and 40 nonhemorrhagic eyes were included in this institutional study. Aqueous humor levels of interleukin (IL)-1b, IL-6, IL-8, IL-10, monocyte chemoattractant protein (MCP)-1, tumor necrosis factor (TNF)-α, vascular endothelial growth factor (VEGF), and soluble VEGF receptor-1 were obtained by multiplex bead assay. Visual acuity and hemorrhage area measurements were obtained, and correlations between cytokine levels and hemorrhage were identified. RESULTS: Levels of MCP-1, TNF-α, and VEGF were higher in hemorrhagic eyes (1506.77 vs. 2131.31 pg/mL, 0.43 vs. 0.63 pg/mL, and 103.96 vs. 206.96 pg/mL; P = 0.050, 0.022, and 0.027, respectively). The levels of IL-8, MCP-1, TNF-α, and VEGF showed positive correlation with visual acuity (P = 0.019, 0.015, 0.001, and 0.014, respectively). The hemorrhage area revealed positive correlation with TNF-α and VEGF levels (P = 0.001 and < 0.001, respectively). CONCLUSION: The presence and amount of hemorrhage in PDR were associated not only with VEGF concentration, but also with the levels of certain inflammatory cytokines, suggesting a role of both VEGF and inflammation in hemorrhagic eyes.

Common risk variants in NPHS1 and TNFSF15 are associated with childhood steroid-sensitive nephrotic syndrome.

To understand the genetics of steroid-sensitive nephrotic syndrome (SSNS), we conducted a genome-wide association study in 987 childhood SSNS patients and 3,206 healthy controls with Japanese ancestry. Beyond known associations in the HLA-DR/DQ region, common variants in NPHS1-KIRREL2 (rs56117924, P=4.94E-20, odds ratio (OR) =1.90) and TNFSF15 (rs6478109, P=2.54E-8, OR=0.72) regions achieved genome-wide significance and were replicated in Korean, South Asian and African populations. Trans-ethnic meta-analyses including Japanese, Korean, South Asian, African, European, Hispanic and Maghrebian populations confirmed the significant associations of variants in NPHS1-KIRREL2 (Pmeta=6.71E-28, OR=1.88) and TNFSF15 (Pmeta=5.40E-11, OR=1.33) loci. Analysis of the NPHS1 risk alleles with glomerular NPHS1 mRNA expression from the same person revealed allele specific expression with significantly lower expression of the transcript derived from the risk haplotype (Wilcox test p=9.3E-4). Because rare pathogenic variants in NPHS1 cause congenital nephrotic syndrome of the Finnish type (CNSF), the present study provides further evidence that variation along the allele frequency spectrum in the same gene can cause or contribute to both a rare monogenic disease (CNSF) and a more complex, polygenic disease (SSNS).

Association of FUT2 and ABO with Crohn's disease in Koreans.

BACKGROUND AND AIM: Fucosyltransferase 2 (FUT2) at 19q13 is a well-established susceptibility locus for Crohn's disease (CD) in Caucasians. FUT2 encodes α-1,2-fucosyltransferase that regulates the secretion of the α-1-2-N-acetylgalactosaminyltransferase and α-1-3-galactosyltransferase (ABO) antigens in both the gastrointestinal mucosa and secretory glands. Given that CD is thought to arise from dysregulated mucosal immune responses to the gut flora and both the ABO blood group and the FUT2 secretor status affect the composition of the gut microbiota, the goal of this study was to evaluate the associations of variants of FUT2 and ABO with CD in Koreans. METHODS: Three single-nucleotide polymorphisms from the FUT2 and ABO genes were genotyped in 1735 patients with CD and 8074 healthy controls. RESULTS: The FUT2 non-secretor allele showed genome-wide significant association with CD in Koreans (rs1047781, odds ratio [OR] = 1.30, Pcombined  = 3.52 × 10-12 ). The ABO locus showed genome-wide significant association with CD in Asians (Pmeta  = 2.35 × 10-8 ). A moderate association was observed with the A and B groups (OR = 1.40, P = 2.26 × 10-6 ; and OR = 1.32, P = 1.92 × 10-4 , respectively) compared with the O group. Following stratification on the basis of FUT2 genotype, carriers of the secretor O blood group were significantly protective against CD than were those of the secretor non-O blood group (OR = 0.63, 95% confidence interval = 0.54-0.73, P = 2.86 × 10-9 ). CONCLUSIONS: These are the first results indicating that the O blood group and FUT2 secretor status are protective factors against CD in Asians.