https://ir.ymlib.yonsei.ac.kr/handle/22282913/181701 Tue, 12 May 2026 22:19:38 GMT 2026-05-12T22:19:38Z https://ir.ymlib.yonsei.ac.kr/handle/22282913/211761 Title: A transferable SARS-CoV-2 IRES module enables dual translation initiation for enhanced antigen expression in COVID-19 mRNA vaccines Authors: Seo, Han Young; Jung, Haewon; Lee, Se-Young; Jung, Hae-Gwang; Son, Yu-Min; Bak, Yeonju; Hwang, Seo-Yeon; Kim, Jung-Hee; Park, In Ho; Shin, Jeon-Soo; Oh, Jong-Won Abstract: mRNA vaccines are a versatile platform for infectious disease prevention and therapeutic applications, yet their performance is limited by exclusive reliance on cap-dependent translation, which is markedly suppressed under hypoxia and cellular stress. Here, we report a hybrid 5 ' untranslated region (5 ' UTR) that enables dual translation initiation via both cap-dependent and internal ribosome entry site (IRES) mechanisms. This element integrates a minimal stem-loop 4.5-5 module (SL4.5-5) from the SARS-CoV-2 genomic 5 ' UTR, in which a conserved 5 '-UUUCGU-3 ' motif within the SL5 loops is essential for function. Incorporating the SL4.5-5 module downstream of conventional 5 ' UTRs confers cap-independent translation capacity and enhances overall translation efficiency under translation-restrictive conditions such as hypoxia. When applied to the 5 ' UTRs of clinically validated COVID-19 vaccines, this module improves antigen expression in both modified and unmodified mRNAs. Notably, unmodified Omicron BA.5 and XBB.1.5 mRNA vaccines containing this element elicited potent humoral and cellular immune responses at sub-microgram doses, comparable to those induced by the approved N1-methylpseu-douridine-incorporated mRNA vaccine, raxtozinameran. These findings identify SL4.5-5 as a modular IRES element that enables dual translation initiation, promoting efficient protein synthesis under cap-dependent translation-restrictive conditions and expanding the functional landscape of mRNA vaccines and therapeutics beyond cap-dependent limitations. Mon, 01 Jun 2026 00:00:00 GMT https://ir.ymlib.yonsei.ac.kr/handle/22282913/211761 2026-06-01T00:00:00Z https://ir.ymlib.yonsei.ac.kr/handle/22282913/212119 Title: Trends in cause-specific mortality among people with and without diabetes in high-income settings: a multinational, population-based study Authors: Magliano, Dianna J.; Morton, Jedidiah, I; Chen, Lei; Sacre, Julian W.; Salim, Agus; Gong, Joanna Y.; Carstensen, Bendix; Gregg, Edward W.; Arffman, Martti; Booth, Gillian L.; Braake, Jonne G. ter; Chu, Luan Manh; Eeg-Olofsson, Katarina; Eliasson, Bjorn; Fleetwood, Kelly; Fosse-Edorh, Sandrine; Garbuviene, Milda; Guion, Marie; Ha, Kyoung Hwa; Kaul, Padma; Ke, Calvin; Keskimaki, Ilmo; Kim, Dae Jung; Laurberg, Tinne; Stovring, Henrik; Vos, Rimke C.; Wild, Sarah H.; Shaw, Jonathan Abstract: Background Cardiovascular disease has historically been the most common cause of death (COD) among people with and without diabetes. However, substantial progress has been made in the management of cardiovascular disease. We conducted a multinational analysis to establish whether this trend is still the case. Methods In this multinational, population-based study, we assembled aggregated annual mortality data collected during routine clinical care from nationally or regionally representative administrative datasets in high-income jurisdictions between 2000 and 2023. For inclusion, datasets must have ongoing enrolment of new patients with diabetes, cause-specific death counts in people with and without diabetes, and sex-specific and age-specific data. We collected population size, counts of prevalent diabetes (type 1 and type 2), death counts, and person-years of follow-up in people with and without diagnosed diabetes by sex and 10-year age group. We estimated cause-specific trends in mortality rates, proportional mortality, and mortality rate ratios (MRR) for people with versus those without diabetes (type 1 and type 2) using Poisson models standardised for age and sex. Findings Using data from 11 jurisdictions, we identified 2 center dot 7 million deaths in people with diabetes and 11 center dot 0 million deaths in people without diabetes during a total of 1 center dot 7 billion person-years of follow-up. Cardiovascular disease mortality decreased in all jurisdictions in populations with and without diabetes. Mean 5-year declines in cardiovascular disease mortality among people with diabetes ranged from 8 center dot 3% (95% CI 5 center dot 9 to 10 center dot 7) to 25 center dot 4% (22 center dot 8 to 28 center dot 0). Mortality due to diabetes declined in most jurisdictions. Dementia mortality increased in people with and without diabetes in six (86%) of seven jurisdictions. Cancer mortality declined in people with diabetes in three (33%) of nine jurisdictions and in people without diabetes in six (67%). At the end of the observation period, cancer was the leading COD in people with diabetes in four (36%) of 11 jurisdictions. MRRs were generally stable for all CODs. Exceptions include Lithuania, where the mean 5-year change in MRR for cardiovascular disease was-7 center dot 6% (-10 center dot 1 to-5 center dot 1), indicating a more rapid fall in cardiovascular disease mortality in people with diabetes than in people without. For dementia, the MRR increased in Denmark (5-year change 8 center dot 0% [5 center dot 0 to 11 center dot 1]) and Scotland (11 center dot 4% [8 center dot 5 to 14 center dot 3]). Interpretation Mortality from cardiovascular disease and diabetes has declined among people with diabetes in most jurisdictions, whereas mortality from dementia has increased markedly, independent of age. Cardiovascular disease is no longer universally the most common COD among people with diabetes in high-income countries. Copyright (c) 2026 Published by Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies. Fri, 01 May 2026 00:00:00 GMT https://ir.ymlib.yonsei.ac.kr/handle/22282913/212119 2026-05-01T00:00:00Z https://ir.ymlib.yonsei.ac.kr/handle/22282913/211240 Title: Korean dioxin risk patterns: Modulation by dietary-socio-demographic and behavioral factors Authors: Lee, Dongjun; Jeong, Kyungjun; Oh, Jeongho; Kim, Changsoo; Park, Seungyoung; Lee, Yongjin Abstract: Background: Dioxins, well-known persistent organic pollutants, accumulate in the human body primarily through dietary exposure. However, it may be significant to examine the current status of dioxin risk in relation to physiological factors, lifestyle factors, and socioeconomic conditions with dietary patterns. Objectives: This study aimed to identify the non-carcinogenic dioxin risk patterns according to physiological, socioeconomic, lifestyle, and dietary factors. Methods: Physiological, socioeconomic, lifestyle, and dietary factors were surveyed for 153 Korean adults (aged 20-59) living in metropolitan areas. 29 dioxin congeners were analyzed in serum samples. The estimated daily dioxin intake was calculated by combining the surveyed dietary consumption data with the dioxin concentrations provided by the Ministry of Food and Drug Safety of Korea. The non-carcinogenic risk from comparing the estimated intake with WHO TDI value was classified into surveyed factors. The association between dietary intake and blood dioxin concentrations was evaluated using a generalized linear model. Results: Females exhibited a higher risk than males, and the risk increased with advancing age. Current smokers showed a lower risk compared to non-smokers and former smokers, while participants with a history of disease demonstrated a notably lower risk than those without such a history. Furthermore, higher monthly income was associated with an increased risk, whereas higher educational attainment was inversely associated with risk. Shellfish was associated with increasing blood DL-PCBs levels. Conclusion: Socio-demographic and behavioral factors may play an important role in modulating the noncarcinogenic risk associated with dietary dioxin exposure. Changes in dioxin risk patterns across such factors warrant further examination through additional investigation. Wed, 01 Apr 2026 00:00:00 GMT https://ir.ymlib.yonsei.ac.kr/handle/22282913/211240 2026-04-01T00:00:00Z https://ir.ymlib.yonsei.ac.kr/handle/22282913/211184 Title: Distinct serum metabolic profiles with supportive diagnostic value in differentiating tuberculosis and Mycobacterium avium complex pulmonary disease Authors: Kim, Keu Eun San; Lee, Ye Jin; Park, Ji Hae; Kwak, Nakwon; Kim, Su-Young; Jhun, Byung Woo; Yim, Jae-Joon; Shin, Sung Jae; 박지해 Abstract: Background: Pulmonary infectious diseases caused by Mycobacterium species, including Mycobacterium tuberculosis and Mycobacterium avium complex (MAC), remain significant public health threats. However, current gold-standard diagnostics are time-consuming and have limited ability to differentiate these clinically similar presentations. This study investigated serum metabolic distinctions between tuberculosis (TB) and MAC pulmonary disease (MAC-PD) to identify biomarkers with supportive diagnostic value for differential diagnosis. Methods: We performed LC/MS-based metabolic profiling of 181 serum samples from TB and MAC-PD patients. The study cohort was subsequently divided into a training set (TB, n = 30; MAC-PD, n = 30) and a validation set (TB, n = 51; MAC-PD, n = 70). Results: Five key metabolites were identified, including four sphingoid base lipids that were decreased in TB compared with MAC-PD, and 2-hydroxyglutaric acid (2-HG), which was increased. Logistic regression using this five-metabolite panel achieved strong discriminatory performance, with an area under the curve of 0.988 (95 % CI: 0.970-1.00 0) in the training set and 0.997 (95 % CI: 0.991-1.00 0) in the validation set. Consistent performance across multiple machine learning models reinforces the stability and supportive diagnostic value of the five-metabolite panel. Conclusions: This study provides a novel approach for the differential diagnosis of two major mycobacterial pulmonary diseases. The identified metabolites, particularly alterations in sphingoid base lipids and 2-HG, demonstrated robust discriminative potential. These findings support their potential role as biomarkers in clinical practice, enabling earlier and more accurate differentiation of TB and MAC-PD. (c) 2026 The Author(s). Published by Elsevier Ltd on behalf of King Saud Bin Abdulaziz University for Health Sciences. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Wed, 01 Apr 2026 00:00:00 GMT https://ir.ymlib.yonsei.ac.kr/handle/22282913/211184 2026-04-01T00:00:00Z