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.

The continuous emergence of SARS-CoV-2 variants as well as other potential future coronavirus has challenged the effectiveness of current COVID-19 vaccines. Therefore, there remains a need for alternative antivirals that target processes less susceptible to mutations, such as the formation of six-helix bundle (6-HB) during the viral fusion step of host cell entry. In this study, a novel high-throughput screening (HTS) assay employing a yeast-two-hybrid (Y2H) system was established to identify inhibitors of HR1/HR2 interaction. The compound IMB-9C, which achieved single-digit micromolar inhibition of SARS-CoV-2 and its Omicron variants with low cytotoxicity, was selected. IMB-9C effectively blocks the HR1/HR2 interaction in vitro and inhibits SARS-CoV-2-S-mediated cell-cell fusion. It binds to both HR1 and HR2 through non-covalent interaction and influences the secondary structure of HR1/HR2 complex. In addition, virtual docking and site-mutagenesis results suggest that amino acid residues A930, I931, K933, T941, and L945 are critical for IMB-9C binding to HR1. Collectively, in this study, we have developed a novel screening method for HR1/HR2 interaction inhibitors and identified IMB-9C as a potential antiviral small molecule against COVID-19 and its variants.

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.

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.

The biological activity of chitinase in degrading chitin has garnered extensive attention,particularly for its potential applications in biological control.This study utilized four spore-form-ing Bacillus strains isolated from Dermacentor nuttalli ticks collected in the Hulunbuir region.Traditional bacterial culture methods were employed for isolation and identification,followed by 16S rRNA sequencing and phylogenetic analysis of the purified cultures.chitin-hydrolyzing strains were screened using colloidal chitin plates,and specific chitinase genes were detected via PCR.Fer-mentation was conducted at 37.0 ℃ for 4 d,and the supernatants were subjected to enzyme activity analysis using the DNS method.Four Gram-positive Bacillus strains were successfully isolated from tick tissue samples,they were identified as B.proteolyticus,B.paramycoides,B.thuringien-sis,and B.cereus,and renamed IMH/B-1,IMH/P-1,IMH/T-1,and IMH/C-1,respectively.PCR a-nalysis detected chitinase genes in B.proteolyticus and B.thuringiensis,while B.cereus and B.pa-ramycoides lacked these genes.However,three strains B.proteolyticus,B.thuringiensis,and B.ce-reus demonstrated significant(P＜0.01)chitin degradation activity on colloidal chitin.Enzyme ac-tivity assays revealed that chitinase activity ranged from 1.292 to 2.032 U/mL,with B.proteolytic-us exhibiting the highest activity 2.032 U/mL,followed by B.cereus 1.496 U/mL and B.thuring-iensis 1.324 U/mL.This study provides a foundation for further research and application of chiti-nase-producing Bacillus strains.

The biological activity of chitinase in degrading chitin has garnered extensive attention,particularly for its potential applications in biological control.This study utilized four spore-form-ing Bacillus strains isolated from Dermacentor nuttalli ticks collected in the Hulunbuir region.Traditional bacterial culture methods were employed for isolation and identification,followed by 16S rRNA sequencing and phylogenetic analysis of the purified cultures.chitin-hydrolyzing strains were screened using colloidal chitin plates,and specific chitinase genes were detected via PCR.Fer-mentation was conducted at 37.0 ℃ for 4 d,and the supernatants were subjected to enzyme activity analysis using the DNS method.Four Gram-positive Bacillus strains were successfully isolated from tick tissue samples,they were identified as B.proteolyticus,B.paramycoides,B.thuringien-sis,and B.cereus,and renamed IMH/B-1,IMH/P-1,IMH/T-1,and IMH/C-1,respectively.PCR a-nalysis detected chitinase genes in B.proteolyticus and B.thuringiensis,while B.cereus and B.pa-ramycoides lacked these genes.However,three strains B.proteolyticus,B.thuringiensis,and B.ce-reus demonstrated significant(P＜0.01)chitin degradation activity on colloidal chitin.Enzyme ac-tivity assays revealed that chitinase activity ranged from 1.292 to 2.032 U/mL,with B.proteolytic-us exhibiting the highest activity 2.032 U/mL,followed by B.cereus 1.496 U/mL and B.thuring-iensis 1.324 U/mL.This study provides a foundation for further research and application of chiti-nase-producing Bacillus strains.

Background: We investigated osteoporosis management strategies and clinical outcomes following the occurrence of medicationrelated osteonecrosis of the jaw (MRONJ). Methods: We retrospectively studied individuals diagnosed with MRONJ during osteoporosis treatment who were managed in the Osteoporosis Center or the Oral Maxillofacial Surgery & Dental Unit at Queen Mary Hospital in Hong Kong between 2010 and 2022. We examined subsequent osteoporosis management plans, fracture events, and bone mineral density (BMD). Results: Thirty-six individuals were included (mean age, 78.5 years; 94.4% women). The estimated prevalence of MRONJ was 0.26%. All patients had been exposed to bisphosphonates, and seven had also received denosumab before MRONJ. Following MRONJ, only 14 individuals continued anti-osteoporosis treatment, a decision influenced by a higher fracture probability at MRONJ onset. The most common regimen was a teriparatide-raloxifene sequence (n=8): three patients achieved stable BMD, four achieved improving BMD, and one exhibited a mixed response. The patient with a mixed BMD response had also been treated with denosumab. Six patients sustained incident fractures after MRONJ, and these patients had lower BMD T-scores than their counterparts. Two patients experienced MRONJ recurrence, which was associated with the resumption of bisphosphonate or denosumab therapy after MRONJ. These patients had higher BMD T-scores than those who did not experience MRONJ recurrence. Conclusion MRONJ is challenging because high fracture risk necessitates discontinuation of antiresorptive agents. Teriparatide followed by raloxifene may be a reasonable regimen. Individualised decisions in osteoporosis management after MRONJ are required to balance fracture risk reduction with minimising MRONJ recurrence.

Objective: Neuroinflammation is suggested to play an important role in the pathophysiology of cognitive impairment. The aim of this study was to investigate the correlation between blood levels of biomarkers and cognitive impairment. Methods: We measured the blood levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and insulin-like growth factor-1 (IGF-1) in a sample of community-residing elderly Koreans (n=37). To evaluate cognitive function, we used the Korean version of the Mini-Mental State Examination (MMSE). We analyzed the association between biomarker levels and the total score, as well as the scores for each domain of the MMSE. Results: We excluded the scores in the three-word registration and naming domains of the MMSE from the analysis, because all participants received perfect scores. The results of simple regression analysis revealed that there is a statistically significant association between higher levels of IL-6 and decreased scores in the repetition domain of the MMSE. However, we found no significant association between TNF-α and IGF-1 levels and the scores of cognitive function tests. Conclusion Our results indicate a potential role of inflammatory cytokines in certain cognitive functions, which requires further exploration.

Objective: The aim of this study was to investigate the association between blood levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and cognitive impairments among elderly individuals. Methods: Peripheral concentration of TNF-α and IL-6 were measured in all subjects. To assess individual cognitive function, the Consortium to Establish a Registry for Alzheimer’s Disease Neuropsychological Assessment Battery (CERAD-NP) was used, and standardized scores (z-scores) were calculated for each test. Cytokine levels were compared between the diagnostic groups, and correlations between blood inflammatory factor levels and z-scores were analyzed. Results: The 37 participants included 8 patients with Alzheimer’s disease (AD), 15 subjects with mild cognitive impairment (MCI), and 14 cognitively healthy controls. TNF-α and IL-6 levels were higher in patients with AD than in healthy controls. TNF-α levels were higher in the AD group than in the MCI group. However, after adjusting for age, the associations between diagnosis and TNF-α and IL-6 were not significant. The higher the plasma IL-6 level, the lower the z-scores on the Boston Naming Test, Word List Learning, Word List Recognition, and Constructional Recall. The higher the serum TNF-α level, the lower the z-scores on the Word List Learning and Constructional Recall. Negative correlation between serum TNF-α level and the z-score on Word List Learning remained significant when age was adjusted. Conclusion The difference in the blood levels of TNF-α and IL-6 between the diagnostic groups may be associated with aging. However, elevated TNF-α levels were associated with worse immediate memory performance, even after adjusting for age.