Purpose: This study aimed to perform a genome characterization of Streptococcus mitis KHUD 011, a strain isolated from the oral microbiome of a healthy Korean individual, and to compare its genomic features with other S. mitis strains. Materials and Methods: The strain was identified through 16S rRNA gene sequencing, and its genome was sequenced using the PacBio Sequel II platform. De novo assembly and annotation were performed, followed by comparative genomic analysis with three additional strains (S. mitis NCTC 12261, S022-V3-A4, and B6). Pan-genome and phylogenetic analyses were conducted to identify strain-specific genes and assess inter-strain genomic diversity. Results: The genome of S. mitis KHUD 011 consisted of 1,782 protein-coding genes, with a G+C content of 40.24%. Pan-genome analysis identified 1,263 core gene clusters (50.0%), 496 dispensable clusters (19.7%), and 763 strain-specific clusters (30.3%). KHUD 011 displayed 88 strain-specific genes, particularly associated with cell wall/membrane biogenesis, transcriptional regulation, and carbohydrate metabolism. Phylogenetic analysis placed KHUD 011 closely with NCTC 12261, forming a distinct cluster apart from other strains. Conclusion The genome characterization of S. mitis KHUD 011 underscores substantial inter-strain genomic diversity influenced by host interactions, ecological niches, and health status. The identified strain-specific genes, particularly those associated with cell wall/ membrane biogenesis, transcriptional regulation, and carbohydrate metabolism, suggest adaptations to the oral microbiome and its interaction with the host. These findings highlight the ecological versatility of S. mitis and the importance of exploring strains from diverse environments to better understand their role within the host and the broader microbiome.

Purpose: This study aimed to perform a genome characterization of Streptococcus mitis KHUD 011, a strain isolated from the oral microbiome of a healthy Korean individual, and to compare its genomic features with other S. mitis strains. Materials and Methods: The strain was identified through 16S rRNA gene sequencing, and its genome was sequenced using the PacBio Sequel II platform. De novo assembly and annotation were performed, followed by comparative genomic analysis with three additional strains (S. mitis NCTC 12261, S022-V3-A4, and B6). Pan-genome and phylogenetic analyses were conducted to identify strain-specific genes and assess inter-strain genomic diversity. Results: The genome of S. mitis KHUD 011 consisted of 1,782 protein-coding genes, with a G+C content of 40.24%. Pan-genome analysis identified 1,263 core gene clusters (50.0%), 496 dispensable clusters (19.7%), and 763 strain-specific clusters (30.3%). KHUD 011 displayed 88 strain-specific genes, particularly associated with cell wall/membrane biogenesis, transcriptional regulation, and carbohydrate metabolism. Phylogenetic analysis placed KHUD 011 closely with NCTC 12261, forming a distinct cluster apart from other strains. Conclusion The genome characterization of S. mitis KHUD 011 underscores substantial inter-strain genomic diversity influenced by host interactions, ecological niches, and health status. The identified strain-specific genes, particularly those associated with cell wall/ membrane biogenesis, transcriptional regulation, and carbohydrate metabolism, suggest adaptations to the oral microbiome and its interaction with the host. These findings highlight the ecological versatility of S. mitis and the importance of exploring strains from diverse environments to better understand their role within the host and the broader microbiome.

Reliable preclinical models for assessing drug-induced cardiotoxicity are essential to reduce the high rate of drug withdrawals during development. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have emerged as a promising platform for such assessments due to their expression of cardiacspecific ion channels and electrophysiological properties. In this study, we investigated the effects of eight arrhythmogenic drugs—E4031, nifedipine, mexiletine, JNJ303, flecainide, moxifloxacin, quinidine, and ranolazine—on hiPSC-CMs derived from both healthy individuals and a long QT syndrome (LQTS) patient using multielectrode array systems. The results demonstrated dose-dependent changes in field potential duration and arrhythmogenic risk, with LQTS-derived hiPSC-CMs showing increased sensitivity to hERG channel blockers such as E4031. Furthermore, the study highlights the potential of hiPSC-CMs to model disease-specific cardiac responses, providing insights into genetic predispositions and personalized drug responses.Despite challenges related to the immaturity of hiPSC-CMs, their ability to recapitulate human cardiac electrophysiology makes them a valuable tool for preclinical cardiotoxicity assessments. This study underscores the utility of integrating patientderived hiPSC-CMs with advanced analytical platforms, such as multi-electrode array systems, to evaluate drug-induced electrophysiological changes. These findings reinforce the role of hiPSC-CMs in drug development, facilitating safer and more efficient screening methods while supporting precision medicine applications.

Background: Active surveillance (AS) has emerged as a viable management strategy for low-risk papillary thyroid microcarcinoma (PTMC), following pioneering trials at Kuma Hospital and the Cancer Institute Hospital in Japan. Numerous prospective cohort studies have since validated AS as a management option for low-risk PTMC, leading to its inclusion in thyroid cancer guidelines across various countries. From 2016 to 2020, the Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) enrolled 1,177 patients, providing comprehensive data on PTMC progression, sonographic predictors of progression, quality of life, surgical outcomes, and cost-effectiveness when comparing AS to immediate surgery. The second phase of MAeSTro (MAeSTro-EXP) expands AS to low-risk papillary thyroid carcinoma (PTC) tumors larger than 1 cm, driven by the hypothesis that overall risk assessment outweighs absolute tumor size in surgical decision-making. Methods: This protocol aims to address whether limiting AS to tumors smaller than 1 cm may result in unnecessary surgeries for low-risk PTCs detected during their rapid initial growth phase. By expanding the AS criteria to include tumors up to 1.5 cm, while simultaneously refining and standardizing the criteria for risk assessment and disease progression, we aim to minimize overtreatment and maintain rigorous monitoring to improve patient outcomes. Conclusion This study will contribute to optimizing AS guidelines and enhance our understanding of the natural course and appropriate management of low-risk PTCs. Additionally, MAeSTro-EXP involves a multinational collaboration between South Korea and Australia. This cross-country study aims to identify cultural and racial differences in the management of low-risk PTC, thereby enriching the global understanding of AS practices and their applicability across diverse populations.

Reliable preclinical models for assessing drug-induced cardiotoxicity are essential to reduce the high rate of drug withdrawals during development. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have emerged as a promising platform for such assessments due to their expression of cardiacspecific ion channels and electrophysiological properties. In this study, we investigated the effects of eight arrhythmogenic drugs—E4031, nifedipine, mexiletine, JNJ303, flecainide, moxifloxacin, quinidine, and ranolazine—on hiPSC-CMs derived from both healthy individuals and a long QT syndrome (LQTS) patient using multielectrode array systems. The results demonstrated dose-dependent changes in field potential duration and arrhythmogenic risk, with LQTS-derived hiPSC-CMs showing increased sensitivity to hERG channel blockers such as E4031. Furthermore, the study highlights the potential of hiPSC-CMs to model disease-specific cardiac responses, providing insights into genetic predispositions and personalized drug responses.Despite challenges related to the immaturity of hiPSC-CMs, their ability to recapitulate human cardiac electrophysiology makes them a valuable tool for preclinical cardiotoxicity assessments. This study underscores the utility of integrating patientderived hiPSC-CMs with advanced analytical platforms, such as multi-electrode array systems, to evaluate drug-induced electrophysiological changes. These findings reinforce the role of hiPSC-CMs in drug development, facilitating safer and more efficient screening methods while supporting precision medicine applications.

Reliable preclinical models for assessing drug-induced cardiotoxicity are essential to reduce the high rate of drug withdrawals during development. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have emerged as a promising platform for such assessments due to their expression of cardiacspecific ion channels and electrophysiological properties. In this study, we investigated the effects of eight arrhythmogenic drugs—E4031, nifedipine, mexiletine, JNJ303, flecainide, moxifloxacin, quinidine, and ranolazine—on hiPSC-CMs derived from both healthy individuals and a long QT syndrome (LQTS) patient using multielectrode array systems. The results demonstrated dose-dependent changes in field potential duration and arrhythmogenic risk, with LQTS-derived hiPSC-CMs showing increased sensitivity to hERG channel blockers such as E4031. Furthermore, the study highlights the potential of hiPSC-CMs to model disease-specific cardiac responses, providing insights into genetic predispositions and personalized drug responses.Despite challenges related to the immaturity of hiPSC-CMs, their ability to recapitulate human cardiac electrophysiology makes them a valuable tool for preclinical cardiotoxicity assessments. This study underscores the utility of integrating patientderived hiPSC-CMs with advanced analytical platforms, such as multi-electrode array systems, to evaluate drug-induced electrophysiological changes. These findings reinforce the role of hiPSC-CMs in drug development, facilitating safer and more efficient screening methods while supporting precision medicine applications.

Background: Active surveillance (AS) has emerged as a viable management strategy for low-risk papillary thyroid microcarcinoma (PTMC), following pioneering trials at Kuma Hospital and the Cancer Institute Hospital in Japan. Numerous prospective cohort studies have since validated AS as a management option for low-risk PTMC, leading to its inclusion in thyroid cancer guidelines across various countries. From 2016 to 2020, the Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) enrolled 1,177 patients, providing comprehensive data on PTMC progression, sonographic predictors of progression, quality of life, surgical outcomes, and cost-effectiveness when comparing AS to immediate surgery. The second phase of MAeSTro (MAeSTro-EXP) expands AS to low-risk papillary thyroid carcinoma (PTC) tumors larger than 1 cm, driven by the hypothesis that overall risk assessment outweighs absolute tumor size in surgical decision-making. Methods: This protocol aims to address whether limiting AS to tumors smaller than 1 cm may result in unnecessary surgeries for low-risk PTCs detected during their rapid initial growth phase. By expanding the AS criteria to include tumors up to 1.5 cm, while simultaneously refining and standardizing the criteria for risk assessment and disease progression, we aim to minimize overtreatment and maintain rigorous monitoring to improve patient outcomes. Conclusion This study will contribute to optimizing AS guidelines and enhance our understanding of the natural course and appropriate management of low-risk PTCs. Additionally, MAeSTro-EXP involves a multinational collaboration between South Korea and Australia. This cross-country study aims to identify cultural and racial differences in the management of low-risk PTC, thereby enriching the global understanding of AS practices and their applicability across diverse populations.

Background: Active surveillance (AS) has emerged as a viable management strategy for low-risk papillary thyroid microcarcinoma (PTMC), following pioneering trials at Kuma Hospital and the Cancer Institute Hospital in Japan. Numerous prospective cohort studies have since validated AS as a management option for low-risk PTMC, leading to its inclusion in thyroid cancer guidelines across various countries. From 2016 to 2020, the Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) enrolled 1,177 patients, providing comprehensive data on PTMC progression, sonographic predictors of progression, quality of life, surgical outcomes, and cost-effectiveness when comparing AS to immediate surgery. The second phase of MAeSTro (MAeSTro-EXP) expands AS to low-risk papillary thyroid carcinoma (PTC) tumors larger than 1 cm, driven by the hypothesis that overall risk assessment outweighs absolute tumor size in surgical decision-making. Methods: This protocol aims to address whether limiting AS to tumors smaller than 1 cm may result in unnecessary surgeries for low-risk PTCs detected during their rapid initial growth phase. By expanding the AS criteria to include tumors up to 1.5 cm, while simultaneously refining and standardizing the criteria for risk assessment and disease progression, we aim to minimize overtreatment and maintain rigorous monitoring to improve patient outcomes. Conclusion This study will contribute to optimizing AS guidelines and enhance our understanding of the natural course and appropriate management of low-risk PTCs. Additionally, MAeSTro-EXP involves a multinational collaboration between South Korea and Australia. This cross-country study aims to identify cultural and racial differences in the management of low-risk PTC, thereby enriching the global understanding of AS practices and their applicability across diverse populations.

Purpose: This study aimed to perform a genome characterization of Streptococcus mitis KHUD 011, a strain isolated from the oral microbiome of a healthy Korean individual, and to compare its genomic features with other S. mitis strains. Materials and Methods: The strain was identified through 16S rRNA gene sequencing, and its genome was sequenced using the PacBio Sequel II platform. De novo assembly and annotation were performed, followed by comparative genomic analysis with three additional strains (S. mitis NCTC 12261, S022-V3-A4, and B6). Pan-genome and phylogenetic analyses were conducted to identify strain-specific genes and assess inter-strain genomic diversity. Results: The genome of S. mitis KHUD 011 consisted of 1,782 protein-coding genes, with a G+C content of 40.24%. Pan-genome analysis identified 1,263 core gene clusters (50.0%), 496 dispensable clusters (19.7%), and 763 strain-specific clusters (30.3%). KHUD 011 displayed 88 strain-specific genes, particularly associated with cell wall/membrane biogenesis, transcriptional regulation, and carbohydrate metabolism. Phylogenetic analysis placed KHUD 011 closely with NCTC 12261, forming a distinct cluster apart from other strains. Conclusion The genome characterization of S. mitis KHUD 011 underscores substantial inter-strain genomic diversity influenced by host interactions, ecological niches, and health status. The identified strain-specific genes, particularly those associated with cell wall/ membrane biogenesis, transcriptional regulation, and carbohydrate metabolism, suggest adaptations to the oral microbiome and its interaction with the host. These findings highlight the ecological versatility of S. mitis and the importance of exploring strains from diverse environments to better understand their role within the host and the broader microbiome.

Reliable preclinical models for assessing drug-induced cardiotoxicity are essential to reduce the high rate of drug withdrawals during development. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have emerged as a promising platform for such assessments due to their expression of cardiacspecific ion channels and electrophysiological properties. In this study, we investigated the effects of eight arrhythmogenic drugs—E4031, nifedipine, mexiletine, JNJ303, flecainide, moxifloxacin, quinidine, and ranolazine—on hiPSC-CMs derived from both healthy individuals and a long QT syndrome (LQTS) patient using multielectrode array systems. The results demonstrated dose-dependent changes in field potential duration and arrhythmogenic risk, with LQTS-derived hiPSC-CMs showing increased sensitivity to hERG channel blockers such as E4031. Furthermore, the study highlights the potential of hiPSC-CMs to model disease-specific cardiac responses, providing insights into genetic predispositions and personalized drug responses.Despite challenges related to the immaturity of hiPSC-CMs, their ability to recapitulate human cardiac electrophysiology makes them a valuable tool for preclinical cardiotoxicity assessments. This study underscores the utility of integrating patientderived hiPSC-CMs with advanced analytical platforms, such as multi-electrode array systems, to evaluate drug-induced electrophysiological changes. These findings reinforce the role of hiPSC-CMs in drug development, facilitating safer and more efficient screening methods while supporting precision medicine applications.