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Purpose Despite the low mortality rate of breast cancer among women in Korea, the breast cancer mortality rate has increased. The aim of this study was to examine trends in breast cancer mortality from 1983 to 2012 in Korea, assessing the importance of age, period, and birth cohort as risk factors. Materials and Methods Data on the annual number of deaths due to female breast cancer and on female population statistics from 1983 to 2012 were obtained from Statistics Korea. A log-linear Poisson ageperiod-cohort model was used to estimate age, period, and cohort effects. Results The increasing breast cancer mortality can be explained predominantly by a birth cohort effect: the risk of breast cancer death showed a steady increase until the 1968 birth cohort, and decreased thereafter. There was a sharp increase in the magnitude of the age effect up to 60 years old, then a moderate increase in the effect during the sixties, followed by another sharp increase from 70 years old. The period effect on breast cancer mortality seems negligible based on its adjusted relative risk, even though it was statistically significant after adjusting for age and cohort effects. Conclusion In this study, the mortality pattern of breast cancer in Korea can be explained predominantly by a birth cohort effect. Hence, the overall mortality rate of breast cancer may increase for a while, and show a gradual decrease in the future, which will start from the younger age group. [ABSTRACT FROM AUTHOR]

Background Higher sunlight exposure is correlated with lower incidence of breast cancer in ecological studies, but findings from prospective studies regarding the association of circulating levels of vitamin D with the risk of breast cancer have been null. The objective of this study was to examine the relation between plasma levels of vitamin D and the risk of postmenopausal breast cancer. Methods We conducted a nested case-control study within the Multiethnic Cohort Study of five race/ethnic groups (white, African-American, Native Hawaiian, Japanese, and Latino) from Hawaii and Los Angeles between 2001 and 2006. Pre-diagnostic plasma levels of 25- hydroxyvitamin D2 [25(OH)D2], 25-hydroxyvitamin D3 [25(OH)D3] and 25(OH)D (sum of 25(OH)D2 and 25(OH)D3) were examined among 707 postmenopausal breast cancer cases and matched controls. Results Using conditional logistic regression models, 20 ng/mL increases of plasma 25(OH)D3 (odds ratio (OR) 0.28; 95% confidence interval (CI) 0.14-0.56) and 25(OH)D (OR 0.43; 95% CI 0.23-0.80) were inversely associated with breast cancer risk among white women, but not among women in other race/ethnic groups. Using two-segmented, piecewise-linear logistic regression models, the change-points of the ORs, either for 25(OH)D3 or for 25(OH)D, were detected as 20 ng/mL among whites. Conclusions Circulating 25(OH)D3 and 25(OH)D were associated with a reduced risk of postmenopausal breast cancer among whites, but not in other ethnic groups, who reside in low latitude regions. [ABSTRACT FROM AUTHOR]

Early vaccination efforts and non-pharmaceutical interventions (NPIs) were insufficient to prevent a surge of COVID-19 cases triggered by the Delta variant. A compartment model that includes age, vaccination, and variants was developed. We estimated the transmission rates using maximum likelihood estimation, and phase-dependent NPIs according to government policies from 26 February to 8 October 2021. Simulations were done to examine the effects of varying dates of initiation and intensity of eased NPIs, arrival timing of Delta, and speed of vaccine administration. The estimated transmission rate matrices show distinct patterns, with transmission rates of younger groups (0-39 years) much larger with Delta. Social distancing (SD) level 2 and SD4 in Korea were associated with transmission reduction factors of 0.63-0.70 and 0.70-0.78, respectively. The easing of NPIs to a level comparable to SD2 should be initiated not earlier than 16 October to keep the number of severe cases below Korea's healthcare capacity. Simulations showed that a surge prompted by Delta can be prevented if the number of people vaccinated daily or SD level when Delta arrived was higher. The timing of easing, intensity of NPIs, vaccination speed, and screening measures are key factors in preventing another epidemic wave. [ABSTRACT FROM AUTHOR]

Neuron subtype dysfunction is a key contributor to neurologic disease circuits, but identifying associated gene regulatory pathways is complicated by the molecular complexity of the brain. For example, parvalbumin-expressing (PV+) neurons in the external globus pallidus (GPe) are critically involved in the motor deficits of dopamine-depleted mouse models of Parkinson's disease, where cell type-specific optogenetic stimulation of PV+ neurons over other neuron populations rescues locomotion. Despite the distinct roles these cell types play in the neural circuit, the molecular correlates remain unknown because of the difficulty of isolating rare neuron subtypes. To address this issue, we developed a new viral affinity purification strategy, Cre-Specific Nuclear Anchored Independent Labeling, to isolate Cre recombinase-expressing (Cre1) nuclei from the adult mouse brain. Applying this technology, we performed targeted assessments of the cell type-specific transcriptomic and epigenetic effects of dopamine depletion on PV+ and PV- cells within three brain regions of male and female mice: GPe, striatum, and cortex. We found GPe PV+ neuron-specific gene expression changes that suggested increased hypoxia-inducible factor 2a signaling. Consistent with transcriptomic data, regions of open chromatin affected by dopamine depletion within GPe PV+ neurons were enriched for hypoxia-inducible factor family binding motifs. The gene expression and epigenomic experiments performed on PV+ neurons isolated by Cre-Specific Nuclear Anchored Independent Labeling identified a transcriptional regulatory network mediated by the neuroprotective factor Hif2a as underlying neural circuit differences in response to dopamine depletion. [ABSTRACT FROM AUTHOR]

Inspired by ultrastructural analysis of ex vivo human tissues as well as the physiological importance of structural density, we fabricated nanogrooves with 1:1, 1:3, and 1:5 spacing ratio (width: spacing, width = 550nm). In response to the nanotopographical density, the adhesion, migration, and differentiation of human mesenchymal stem cells (hMSCs) were sensitively controlled, but the proliferation showed no significant difference. In particular, the osteo- or neurogenesis of hMSCs were enhanced at the 1:3 spacing ratio rather than 1:1 or 1:5 spacing ratio, implying an existence of potentially optimized nanotopographical density for stem cell function. Furthermore, such cellular behaviors were positively correlated with several cell morphological indexes as well as the expression of integrin β1 or N-cadherin. Our findings propose that nanotopographical density may be a key parameter for the design and manipulation of functional scaffolds for stem cell-based tissue engineering and regenerative medicine. [ABSTRACT FROM AUTHOR]

Background: Triple-negative breast cancers (TNBCs) and basal-like breast cancers (BLBCs) are known as poor outcome subtypes with a lack of targeted therapy. Previous studies have shown conflicting results regarding the difference of prognostic significance between TNBCs and BLBCs. In this study, we aimed to characterize the prognostic features of TNBCs, in view of BLBCs and quintuple-negative breast cancers (QNBC/5NPs). Methods: Using tissue microarray-based immunohistochemical analysis, we categorized 951 primary breast cancers into four or five subtypes according to the expression of ER, PR, HER2, and basal markers (CK5/6, EGFR). Results: The results of this study showed that both TNBCs and BLBCs were associated with high histological and/ or nuclear grades. When the TNBCs are divided into two subtypes by the presence of basal markers, the clinicopathologic characteristics of TNBCs were mainly maintained in the BLBCs. The 5-subgrouping was the better prediction model for both disease free and overall survival in breast cancers than the 4-subgrouping. After multivariate analysis of TNBCs, the BLBCs did not have a worse prognosis than the QNBC/5NPs. Interestingly, the patients with BLBCs showed significant adjuvant chemotherapy benefit. In addition, QNBC/5NPs comprised about 6∼8% of breast cancers in publicly available breast cancer datasets Conclusion: The QNBC/5NP subtype is a worse prognostic subgroup of TNBCs, especially in higher stage and this result may be related to adjuvant chemotherapy benefit of BLBCs, calling for caution in the identification of subgroups of patients for therapeutic classification. [ABSTRACT FROM AUTHOR]

In this study, our aim was to investigate the association of inflammation-related genetic polymorphisms and gastric cancer risk and to examine whether the combined effect of soybean product intake modified cancer risk. Eighty-four incident gastric cancer cases and 336 matched controls were selected from the Korean Multi-Center Cancer Cohort. We selected 14 single nucleotide polymorphisms (SNP) from 5 genes [interleukin IL)-1β, IL-2, IL-4, IL-8, and IL-10] and used unconditional logistic regression model to calculate the odds ratios (OR) and 95% CI adjusting for H. pyloriseropositivity, smoking, age, sex, enrollment year, and residential area. The risk for gastric cancer in relation to genetic polymorphisms and haplotypes were assessed according to soybean product intake levels. Although no single SNP effect was found, the combined effect between IL-10 gene variants of -592 GG/GA, -819 TC/CC, or - 1082 AG/GG and low intake of soybean products had an increased risk for gastric cancer compared with the group with no risk gene variants and a high intake of soybean products (OR [95% CI] = 2.82 [1.04-7.62], 2.75 [1.02-7.44], and 4.34 [1.51-12.5], respectively). Among the low- soybean product intake group, IL-10 CCG haplotype had an increased risk of gastric cancer (OR = 3.38 [1.40-8.13]) relative to the ATA haplotype. Our results suggest that the association between IL-b genetic polymorphisms and gastric cancer risk was modified by soybean product intake. [ABSTRACT FROM AUTHOR]

‘Healthy Twin’ is a twin family study extension of the existing Korean Twin-Family Register. Healthy Twin recruits adult like-sex twins over the age of 30 and their adult family members. Healthy Twin protocols are primarily tailored to the study of the quantitative trait loci of complex traits as well as to the role of environment in the etiology of complex diseases. A full-length survey is underway, including questionnaires, health examinations and the collection of biological specimens. So far, 820 individuals (169 twin pairs and their families) have participated in the survey and 1068 individual twins (608 twin pairs) have replied to the mailed zygosity questionnaire as of July 2006. The first phase (2005–2006) of Healthy Twin will recruit 1550 individuals (including about 380 twin pairs), and the second phase a proposed 1500 to 2500 additional participants. We report study protocols and zygosity and the distribution of family size of the study participants. [ABSTRACT FROM AUTHOR]

A correction to the article "Triple-negative, basal-like, and quintuple-negative breast cancers: Better prediction model for survival," is presented.