Socioeconomic Inequalities in Adolescent Depression in South Korea: A Multilevel Analysis

Background: In recent years, South Korea has witnessed a sustained rise in the prevalence of adolescent depression. In the present study, we sought to investigate family and school environmental influences on adolescent depression. Methods and Findings Middle and high school students (N = 75,066) were randomly selected respondents to a web-based survey and answered questions on their academic and socioeconomic backgrounds, parental support, parental education level, physical activities, lifestyle habits and their experience of depression in the past one year. Two-level multilevel analysis was used to investigate the relationship between depression and individual (level 1) and school (level 2) factors. Girls reported having experienced depression in greater numbers than boys (43.96% vs. 32.03%). A significant association was found between adolescent depression experience and gender, grade, self-rated academic achievement, family affluence scale, parental support, parental education level, lifestyle habits, physical activity and sleep dissatisfaction. The students living with rich parents were more likely to be depressive, and maternal higher education was significantly associated with higher probability of boys’ depression experience. Low academic achievement was highly associated with the experience of depression. In school level contexts, girls were found to be less likely to be depressive in girls-only schools. Conclusion: The adolescent depression experience is not only an individual phenomenon but is highly associated with other factors such as parents, peers, academic achievement, and even gender mix in the school. Thus, prevention measures on youth depression need to focus on emphasizing less pressure from parents on academic performance, and establishing healthy inter-gender relationships within co-education schools

Transcriptional regulatory networks of tumor-associated macrophages that drive malignancy in mesenchymal glioblastoma.

BACKGROUND: Glioblastoma (GBM) is a complex disease with extensive molecular and transcriptional heterogeneity. GBM can be subcategorized into four distinct subtypes; tumors that shift towards the mesenchymal phenotype upon recurrence are generally associated with treatment resistance, unfavorable prognosis, and the infiltration of pro-tumorigenic macrophages. RESULTS: We explore the transcriptional regulatory networks of mesenchymal-associated tumor-associated macrophages (MA-TAMs), which drive the malignant phenotypic state of GBM, and identify macrophage receptor with collagenous structure (MARCO) as the most highly differentially expressed gene. MARCO CONCLUSIONS: Collectively, our study characterizes the global transcriptional profile of TAMs driving mesenchymal GBM pathogenesis, providing potential therapeutic targets for improving the effectiveness of GBM immunotherapy

Association of Serum 25-Hydroxyvitamin D Levels with Markers for Metabolic Syndrome in the Elderly: A Repeated Measure Analysis

The purpose of current study was to investigate associations of serum 25-hydroxyvitamin D (OHVD) levels with markers for metabolic syndrome in elderly Koreans. We conducted a panel study on 301 individuals over 60 yr old in Seoul, Korea, and repeatedly measured serum OHVD, glucose, insulin, and lipid levels. Mixed effect model and generalized estimating equations were used to investigate relationships between serum OHVD levels with marker levels for metabolic syndrome and each of its categories. Of all subjects, 76.6% were vitamin D deficient (< 50 nM) and 16.9% were insufficient (< 75 nM). Inverse association was demonstrated between serum OHVD levels and insulin (P = 0.004), triglyceride (P = 0.023) and blood pressure (systolic blood pressure: P = 0.002; diastolic blood pressure: P < 0.001). Vitamin D deficiency was found to increase risk of 'hypertriglyceridemia' category of metabolic syndrome (odds ratio: 1.73, 95% confidence interval: 1.13-2.66). In conclusion, we found from our repeated measure analysis that decreasing serum OHVD levels are associated with increasing insulin resistance, increasing serum triglyceride levels and increasing blood pressure in elderly Koreans, and confirmed on the risk of 'hypertriglyceridemia' in vitamin D deficient subjects

An Engineered Viral Protease Exhibiting Substrate Specificity for a Polyglutamine Stretch Prevents Polyglutamine-Induced Neuronal Cell Death

BACKGROUND: Polyglutamine (polyQ)-induced protein aggregation is the hallmark of a group of neurodegenerative diseases, including Huntington's disease. We hypothesized that a protease that could cleave polyQ stretches would intervene in the initial events leading to pathogenesis in these diseases. To prove this concept, we aimed to generate a protease possessing substrate specificity for polyQ stretches. METHODOLOGY/PRINCIPAL FINDINGS: Hepatitis A virus (HAV) 3C protease (3CP) was subjected to engineering using a yeast-based method known as the Genetic Assay for Site-specific Proteolysis (GASP). Analysis of the substrate specificity revealed that 3CP can cleave substrates containing glutamine at positions P5, P4, P3, P1, P2', or P3', but not substrates containing glutamine at the P2 or P1' positions. To accommodate glutamine at P2 and P1', key residues comprising the active sites of the S2 or S1' pockets were separately randomized and screened. The resulting sets of variants were combined by shuffling and further subjected to two rounds of randomization and screening using a substrate containing glutamines from positions P5 through P3'. One of the selected variants (Var26) reduced the expression level and aggregation of a huntingtin exon1-GFP fusion protein containing a pathogenic polyQ stretch (HttEx1(97Q)-GFP) in the neuroblastoma cell line SH-SY5Y. Var26 also prevented cell death and caspase 3 activation induced by HttEx1(97Q)-GFP. These protective effects of Var26 were proteolytic activity-dependent. CONCLUSIONS/SIGNIFICANCE: These data provide a proof-of-concept that proteolytic cleavage of polyQ stretches could be an effective modality for the treatment of polyQ diseases

Multicenter retrospective analysis of 581 patients with primary intestinal non-hodgkin lymphoma from the Consortium for Improving Survival of Lymphoma (CISL)

<p>Abstract</p> <p>Background</p> <p>Primary intestinal non-Hodgkin lymphoma (NHL) is a heterogeneous disease with regard to anatomic and histologic distribution. Thus, analyses focusing on primary intestinal NHL with large number of patients are warranted.</p> <p>Methods</p> <p>We retrospectively analyzed 581 patients from 16 hospitals in Korea for primary intestinal NHL in this retrospective analysis. We compared clinical features and treatment outcomes according to the anatomic site of involvement and histologic subtypes.</p> <p>Results</p> <p>B-cell lymphoma (n = 504, 86.7%) was more frequent than T-cell lymphoma (n = 77, 13.3%). Diffuse large B-cell lymphoma (DLBCL) was the most common subtype (n = 386, 66.4%), and extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) was the second most common subtype (n = 61, 10.5%). B-cell lymphoma mainly presented as localized disease (Lugano stage I/II) while T-cell lymphomas involved multiple intestinal sites. Thus, T-cell lymphoma had more unfavourable characteristics such as advanced stage at diagnosis, and the 5-year overall survival (OS) rate was significantly lower than B-cell lymphoma (28% versus 71%, P < 0.001). B symptoms were relatively uncommon (20.7%), and bone marrow invasion was a rare event (7.4%). The ileocecal region was the most commonly involved site (39.8%), followed by the small (27.9%) and large intestines (21.5%). Patients underwent surgery showed better OS than patients did not (5-year OS rate 77% versus 57%, P < 0.001). However, this beneficial effect of surgery was only statistically significant in patients with B-cell lymphomas (P < 0.001) not in T-cell lymphomas (P = 0.460). The comparison of survival based on the anatomic site of involvement showed that ileocecal regions had a better 5-year overall survival rate (72%) than other sites in consistent with that ileocecal region had higher proportion of patients with DLBCL who underwent surgery. Age > 60 years, performance status ≥ 2, elevated serum lactate dehydrogenase, Lugano stage IV, presence of B symptoms, and T-cell phenotype were independent prognostic factors for survival.</p> <p>Conclusions</p> <p>The survival of patients with ileocecal region involvement was better than that of patients with involvement at other sites, which might be related to histologic distribution, the proportion of tumor stage, and need for surgical resection.</p

Review and consensus recommendations on clinical APT-weighted imaging approaches at 3T: Application to brain tumors

Amide proton transfer-weighted (APTw) MR imaging shows promise as a biomarker of brain tumor status. Currently used APTw MRI pulse sequences and protocols vary substantially among different institutes, and there are no agreed-on standards in the imaging community. Therefore, the results acquired from different research centers are difficult to compare, which hampers uniform clinical application and interpretation. This paper reviews current clinical APTw imaging approaches and provides a rationale for optimized APTw brain tumor imaging at 3T, including specific recommendations for pulse sequences, acquisition protocols, and data processing methods. We expect that these consensus recommendations will become the first broadly accepted guidelines for APTw imaging of brain tumors on 3 T MRI systems from different vendors. This will allow more medical centers to use the same or comparable APTw MRI techniques for the detection, characterization, and monitoring of brain tumors, enabling multi-center trials in larger patient cohorts and, ultimately, routine clinical use

Identification and Validation of Novel Cerebrospinal Fluid Biomarkers for Staging Early Alzheimer's Disease

Ideally, disease modifying therapies for Alzheimer disease (AD) will be applied during the 'preclinical' stage (pathology present with cognition intact) before severe neuronal damage occurs, or upon recognizing very mild cognitive impairment. Developing and judiciously administering such therapies will require biomarker panels to identify early AD pathology, classify disease stage, monitor pathological progression, and predict cognitive decline. To discover such biomarkers, we measured AD-associated changes in the cerebrospinal fluid (CSF) proteome.CSF samples from individuals with mild AD (Clinical Dementia Rating [CDR] 1) (n = 24) and cognitively normal controls (CDR 0) (n = 24) were subjected to two-dimensional difference-in-gel electrophoresis. Within 119 differentially-abundant gel features, mass spectrometry (LC-MS/MS) identified 47 proteins. For validation, eleven proteins were re-evaluated by enzyme-linked immunosorbent assays (ELISA). Six of these assays (NrCAM, YKL-40, chromogranin A, carnosinase I, transthyretin, cystatin C) distinguished CDR 1 and CDR 0 groups and were subsequently applied (with tau, p-tau181 and Aβ42 ELISAs) to a larger independent cohort (n = 292) that included individuals with very mild dementia (CDR 0.5). Receiver-operating characteristic curve analyses using stepwise logistic regression yielded optimal biomarker combinations to distinguish CDR 0 from CDR>0 (tau, YKL-40, NrCAM) and CDR 1 from CDR<1 (tau, chromogranin A, carnosinase I) with areas under the curve of 0.90 (0.85-0.94 95% confidence interval [CI]) and 0.88 (0.81-0.94 CI), respectively.Four novel CSF biomarkers for AD (NrCAM, YKL-40, chromogranin A, carnosinase I) can improve the diagnostic accuracy of Aβ42 and tau. Together, these six markers describe six clinicopathological stages from cognitive normalcy to mild dementia, including stages defined by increased risk of cognitive decline. Such a panel might improve clinical trial efficiency by guiding subject enrollment and monitoring disease progression. Further studies will be required to validate this panel and evaluate its potential for distinguishing AD from other dementing conditions

Genetic drivers of heterogeneity in type 2 diabetes pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P &lt; 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care.</p