Clinical and Radiologic Predictors of Response to Atezolizumab-Bevacizumab in Advanced Hepatocellular Carcinoma.

Purpose: This study aimed to identify clinical and radiologic characteristics that could predict response to atezolizumab-bevacizumab combination therapy in patients with advanced hepatocellular carcinoma (HCC). Materials and Methods: This single-center retrospective study included 108 advanced HCC patients with intrahepatic lesions who were treated with atezolizumab-bevacizumab. Two radiologists independently analyzed Imaging characteristics of the index tumor on pretreatment computed tomography. Predictive factors associated with progressive disease (PD) at the best response based on Response Evaluation Criteria in Solid Tumors, Version 1.1 were evaluated using logistic regression analysis. Progression-free survival (PFS) was estimated by the Kaplan-Meier method and compared with the log-rank test. Results: Of 108 patients with a median PFS of 15 weeks, 40 (37.0%) had PD during treatment. Factors associated with PD included the presence of extrahepatic metastases (adjusted odds ratio [aOR], 4.13; 95% confidence interval [CI], 1.19-14.35; p=0.03), the infiltrative appearance of the tumor (aOR, 3.07; 95% CI, 1.05-8.93; p=0.04), and the absence of arterial phase hyperenhancement (APHE) (aOR, 6.34; 95% CI, 2.18-18.47; p<0.001). Patients with two or more of these factors had a PD of 66.7% and a median PFS of 8 weeks, indicating a significantly worse outcome compared to the patients with one or no of these factors. Conclusion: In patients with advanced HCC treated with atezolizumab-bevacizumab treatment, the absence of APHE, infiltrative appearance of the intrahepatic tumor, and presence of extrahepatic metastases were associated with poor response and survival. Evaluation of early response may be necessary in patients with these factors.

Persistent differences in the immunogenicity of the two COVID-19 primary vaccines series, modulated by booster mRNA vaccination and breakthrough infection.

INTRODUCTION: The long-term impact of initial immunogenicity induced by different primary COVID-19 vaccine series remains unclear. METHODS: A prospective cohort study was conducted at 10 tertiary hospitals in Korea from March 2021 to September 2022. Immunogenicity assessments included anti-spike protein antibody (Sab), SARS-CoV-2-specific interferon-gamma releasing assay (IGRA), and multiplex cytokine assays for spike protein-stimulated plasma. Spike proteins derived from wild-type SARS-CoV-2 and alpha variant (Spike1) and beta and gamma variant (Spike2) were utilized. RESULTS: A total of 235 healthcare workers who had received a two-dose primary vaccine series of either ChAdOx1 or BNT162b2, followed by a third booster dose of BNT162b2 (166 in the ChAdOx1/ChAdOx1/BNT162b2 (CCB) group and 69 in the BNT162b2/BNT162b2/BNT162b2 (BBB) group, based on the vaccine series) were included. Following the primary vaccine series, the BBB group exhibited significantly higher increases in Sab levels, IGRA responses, and multiple cytokines (CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1ß, interleukin (IL)-1ra, IFN-γ, IL-2, IL-4, and IL-10) compared to the CCB group (all P < 0.05). One month after the third BNT162b2 booster, the CCB group showed Sab levels comparable to those of the BBB group, and both groups exhibited lower levels after six months without breakthrough infections (BIs). However, among those who experienced BA.1/2 BIs after the third booster, Sab levels increased significantly more in the BBB group than in the CCB group (P < 0.001). IGRA responses to both Spike1 and Spike2 proteins were significantly stronger in the BBB group than the CCB group after the third booster, while only the Spike2 response were higher after BIs (P = 0.007). The BBB group exhibited stronger enhancement of T-cell cytokines (IL-2, IL-4, and IL-17A) after BIs than in the CCB group (P < 0.05). CONCLUSION: Differences in immunogenicity induced by the two primary vaccine series persisted, modulated by subsequent booster vaccinations and BIs.

Effectiveness of COVID-19 XBB.1.5 monovalent mRNA vaccine in Korea: interim analysis.

As coronavirus disease-2019 (COVID-19) becomes an endemic disease, the virus continues to evolve and become immunologically distinct from previous strains. Immune imprinting has raised concerns about bivalent mRNA vaccines containing both ancestral virus and Omicron variant. To increase efficacy against the predominant strains as of the second half of 2023, the updated vaccine formulation contained only the mRNA of XBB.1.5 sublineage. We conducted a multicenter, test-negative, case-control study to estimate XBB.1.5 monovalent vaccine effectiveness (VE) and present the results of an interim analysis with data collected in November 2023. Patients who underwent COVID-19 testing at eight university hospitals were included and matched based on age (19-49, 50-64, and ≥65 years) and sex in a 1:1 ratio. VE was calculated using the adjusted odds ratio derived from multivariable logistic regression. Of the 992 patients included, 49 (5.3%) received the XBB.1.5 monovalent vaccine at least 7 days before COVID-19 testing. Patients with COVID-19 (cases) were less likely to have received the XBB.1.5 monovalent vaccine (case 3.5% vs. control 7.2%, p=0.019) and to have a history of COVID-19 within 6 months (2.2% vs. 4.6%, p=0.068). In contrast, patients with COVID-19 were more likely to be healthcare workers (8.2% vs. 3.0%, p=0.001) and to have chronic neurological diseases (16.7% vs. 11.9%, p=0.048). The adjusted VE of the XBB.1.5 monovalent mRNA vaccine was 56.8% (95% confidence interval: 18.7-77.9%). XBB.1.5 monovalent mRNA vaccine provided significant protection against COVID-19 in the first one to two months after vaccination.

plantMASST - Community-driven chemotaxonomic digitization of plants.

Understanding the distribution of hundreds of thousands of plant metabolites across the plant kingdom presents a challenge. To address this, we curated publicly available LC-MS/MS data from 19,075 plant extracts and developed the plantMASST reference database encompassing 246 botanical families, 1,469 genera, and 2,793 species. This taxonomically focused database facilitates the exploration of plant-derived molecules using tandem mass spectrometry (MS/MS) spectra. This tool will aid in drug discovery, biosynthesis, (chemo)taxonomy, and the evolutionary ecology of herbivore interactions.

Increased Active Inflammation in the Colon is Not a Reliable Predictor of an Elevated Risk of Dysplasia in Patients With Primary Sclerosing Cholangitis and Ulcerative Colitis.

Although the increased risk of colorectal neoplasia in patients with both primary sclerosing cholangitis (PSC) and ulcerative colitis (UC; termed PSC-UC) is well documented, the mechanism through which concomitant PSC increases the risk of colorectal neoplasia remains unclear. Given that the risk of colorectal neoplasia in UC is positively correlated with increased histologic inflammation, this study sought to investigate whether increased histologic inflammation could be used to stratify the risk of dysplasia development in patients with PSC-UC. Twenty patients with PSC-UC and dysplasia were compared with 30 control patients with PSC-UC who had no history of neoplasia. For each patient, all surveillance biopsies were scored using a 4-point scoring system: (1) no epithelial neutrophils = 0, (2) cryptitis only = 1, (3) cryptitis plus crypt abscess in <50% of crypts = 2, and (4) crypt abscess in ≥50% of crypts, erosion, neutrophilic exudate, and/or ulceration = 3. A score was designated for each biopsy, and both mean and maximum inflammation scores were calculated from all biopsies taken during each colonoscopy. The inflammation burden score was calculated for each surveillance interval by multiplying the average maximum score between each pair of surveillance episodes by the length of the surveillance interval in years. The average scores derived from all colonoscopies for each patient were used to determine the patient's overall mean, maximum, and inflammation burden scores. In both the dysplasia and control groups, the 3 summative inflammation scores were calculated independently for the entire colon, right colon, and left colon. The dysplasia group consisted of 14 (70%) men and 6 (30%) women, with a mean age of 27 years at UC diagnosis and a long history of pancolitis (mean duration: 17 y). A total of 49 dysplastic lesions were detected in the dysplasia group, and 8 (40%) of the 20 patients had multifocal dysplasia. The majority of dysplastic lesions belonged to nonconventional subtypes (n = 28; 57%) and were located in the right colon (n = 37; 76%). Irrespective of the colon segment, there was no significant difference in the 3 summative inflammation scores between the dysplasia and control groups (P > 0.05). However, in each group, the 3 summative inflammation scores were significantly higher in the right colon than in the left colon (P< 0.05). In conclusion, patients with PSC-UC exhibit increased histologic inflammation in the right colon compared with the left colon, regardless of the presence of dysplasia. Although this may provide an explanation for the predominance of right-sided colorectal neoplasia in patients with PSC-UC, increased histologic inflammation does not reliably predict an elevated risk of dysplasia in patients with PSC-UC. These findings reinforce the current recommendation for annual endoscopic surveillance for all patients with PSC-UC, irrespective of the extent and severity of inflammation.

Extraskeletal Ewing Sarcoma of the Gastrointestinal and Hepatobiliary Tract: Deceptive Immunophenotype Commonly Leads to Misdiagnosis.

Ewing sarcoma (ES) is an uncommon mesenchymal neoplasm that typically develops as a bone mass, although up to 30% arise in extraskeletal sites. ES of the gastrointestinal (GI) and hepatobiliary tract is rare and may be misdiagnosed as other, more common neoplasms that occur in these sites. However, the correct classification of extraskeletal ES is important for timely clinical management and prognostication. We reviewed our experience of ES in the GI and hepatobiliary tract in order to further highlight the clinicopathologic features of these neoplasms and document the potential for misdiagnosis in this setting. The archives and consultation files of 6 academic institutions were retrospectively queried for cases of ES occurring in the GI and hepatobiliary tract. The histologic slides and ancillary studies were reviewed and clinical data were retrieved for each case through the electronic medical records, when available. Twenty-three patients with ES in the GI and/or hepatobiliary tract were identified from 2000 to 2022. Of these, 11 were women and 12 were men with a median age of 38 years (range, 2 to 64). Tumor locations included the pancreas (n=5), liver (n=2), stomach (n=3), colorectum (n=3), and small intestine (n=5), as well as tumors involving multiple organs, pelvis and retroperitoneum (n=5). Tumor size varied between 2 cm and 18 cm. Twenty were primary and 3 were metastases. Of the 23 cases, only 17% were initially diagnosed as ES. The most common misdiagnoses involved various forms of neuroendocrine neoplasia due to expression of synaptophysin and other neuroendocrine markers (22%). A wide variety of diagnoses including GI stromal tumor was considered due to aberrant CD117 expression (4%). The diagnosis of ES was ultimately confirmed by detection of the EWSR1 rearrangement in 22 cases. The remaining case was diagnosed using traditional immunohistochemistry. Follow-up information was available in 20 cases, with follow-up time varying between 2 and 256 months. Six patients with follow-up died of disease between 6 and 60 months following initial presentation. Our data indicate ES in the GI and hepatobiliary tract is commonly misdiagnosed leading to a delay in therapy. In light of the attendant therapeutic and prognostic implications, ES should be considered in the differential diagnosis of any GI or hepatobiliary tumor with epithelioid and/or small round cell morphology.

Pregnancy related complications in women with hypertrophic cardiomyopathy: a nationwide population-based cohort study.

BACKGROUND: The impact of hypertrophic cardiomyopathy (HCM) on cardiovascular and obstetrical outcomes in pregnant women remains unclear, particularly in Asian populations. This study aimed to evaluate the maternal cardiovascular and obstetrical outcomes in Korean women with HCM. METHODS: Using data from the Korean National Health Insurance Service database, we identified women who gave birth via cesarean section or vaginal delivery after being diagnosed with HCM between 2006 and 2019. Maternal cardiovascular and obstetrical outcomes were assessed based on the trimester of pregnancy. RESULTS: This study included 122 women and 158 pregnancies. No maternal deaths were noted; however, 21 cardiovascular events, such as hospital admission for cardiac problems, including heart failure and atrial fibrillation (AF), new-onset AF or ventricular tachycardia (VT) occurred in 14 pregnancies (8.8%). Cardiac events occurred throughout pregnancy with a higher occurrence in the third trimester. Cesarean sections were performed in 49.3% of the cases, and all cardiovascular outcomes occurring after delivery were observed in patients who had undergone cesarean sections. Seven cases involved preterm delivery, and two of these cases were accompanied by cardiac events, specifically AF. Pre-existing arrhythmia (AF: odds ratio (OR): 7.44, 95% confidence interval (CI): 2.61-21.21, P < 0.001; VT: OR: 31.61, 95% CI: 5.85-172.77, P < 0.001) was identified as a predictor for composite outcomes of cardiovascular events or preterm delivery. CONCLUSIONS: Most pregnant women with HCM were well-tolerated. However, cardiovascular complications could occur in some patients. Therefore, planned delivery may be necessary for selected patients, especially the women with pre-existing arrhythmias.

Follow-up biopsies in gastrointestinal immune checkpoint inhibitor toxicity may show markedly different inflammatory patterns than initial injury.

Colitis is a common manifestation of immune checkpoint inhibitor (ICI) toxicity and can present with varied histologic patterns of inflammation, some of which have been shown to be associated with specific ICI drug types. Although the histologic features of ICI colitis seen at the time of diagnosis have been described, there have been few reports following these patients over time. We evaluated initial and follow-up biopsies in 30 patients with ICI colitis and found that 37% of patients developed a different pattern of injury on follow-up biopsy compared to the initial biopsy. Patients with a different inflammatory pattern were more likely to have restarted ICI therapy before their follow-up biopsy (64%) compared to those without a change in inflammatory pattern (11%; P < 0.01). The majority of these patients had changed ICI drug types (86%). Additionally, many cases changed to an inflammatory bowel disease (IBD)-like pattern (36%), raising a question of de novo IBD. However, all of our patients with an IBD-like pattern experienced sustained resolution of symptoms without steroids or other immunosuppressive medications following discontinuation of ICI therapy, consistent with a diagnosis of ICI toxicity. Our findings suggest that follow-up biopsies in patients with ICI colitis may show a different histology and that this does not necessarily warrant a change in the histologic diagnosis to another disease.

Updated Reference Intervals for Alanine Aminotransferase in a Metabolically and Histologically Normal Population.

BACKGROUND AND AIMS: This study aims to reevaluate upper reference limit (URL) for alanine aminotransferase (ALT) by considering the changing epidemiology of major liver diseases. We employed histological and metabolic parameters in Asian living liver donors. METHODS: We performed a retrospective analysis of 5,455 potential living liver donors from 2005 to 2019. Participants were screened for hepatitis B, C, HIV, and alcohol use. Histologically and metabolically healthy participants were assessed using the Prati criteria (body mass index <23 kg/m2, triglyceride ≤200 mg/dL, fasting glucose ≤105 mg/dL, total cholesterol ≤220 mg/dL). The updated ALT-URL was determined as the 95th percentile among participants without hepatic steatosis and who met the Prati criteria. RESULTS: The median age was 30 years, with a male predominance (66.2%). Among 5,455 participants, 3,162 (58.0%) showed no hepatic steatosis, with 1,553 (49.1%) meeting both the criteria for no steatosis and the Prati criteria for metabolic health. The updated URL for ALT in these participants was 34 U/L for males and 22 U/L for females, which was significantly lower than conventionally accepted values. Using this revised ALT-URL, 72.8% of males with ALT levels ≥34 U/L and 55.0% of females with ALT levels ≥22 U/L showed signs of steatosis, while 32.7% of males and 22.2% of females met the criteria for metabolic syndrome. CONCLUSIONS: Our study provided the newly established reference intervals for ALT levels in a metabolically and histologically verified Asian population. The proposed URL for ALT are 34 U/L and 22 U/L for males and females, respectively.

Cytoplasmic Ca2+ influx mediates iron- and reactive oxygen species-dependent ferroptotic cell death in rice immunity.

Iron- and reactive oxygen species (ROS)-dependent ferroptosis occurs in plant cells. Ca2+ acts as a conserved key mediator to control plant immune responses. Here, we report a novel role of cytoplasmic Ca2+ influx regulating ferroptotic cell death in rice immunity using pharmacological approaches. High Ca2+ influx triggered iron-dependent ROS accumulation, lipid peroxidation, and subsequent hypersensitive response (HR) cell death in rice (Oryza sativa). During Magnaporthe oryzae infection, 14 different Ca2+ influx regulators altered Ca2+, ROS and Fe2+ accumulation, glutathione reductase (GR) expression, glutathione (GSH) depletion and lipid peroxidation, leading to ferroptotic cell death in rice. High Ca2+ levels inhibited the reduction of glutathione isulphide (GSSG) to GSH in vitro. Ca2+ chelation by ethylene glycol-bis (2-aminoethylether)-N, N, N', N'-tetra-acetic acid (EGTA) suppressed apoplastic Ca2+ influx in rice leaf sheaths during infection. Blocking apoplastic Ca2+ influx into the cytoplasm by Ca2+ chelation effectively suppressed Ca2+-mediated iron-dependent ROS accumulation and ferroptotic cell death. By contrast, acibenzolar-S-methyl (ASM), a plant defense activator, significantly enhanced Ca2+ influx, as well as ROS and iron accumulation to trigger ferroptotic cell death in rice. The cytoplasmic Ca2+ influx through calcium-permeable cation channels, including the putative resistosomes, could mediate iron- and ROS-dependent ferroptotic cell death under reduced GR expression levels in rice immune responses.

High risk features in colorectal adenomatous polyps: A multi-institutional study.

High risk features in colorectal adenomatous polyps include size >1 cm and advanced histology: high-grade dysplasia and villous architecture. We investigated whether the diagnostic rates of advanced histology in colorectal adenomatous polyps were similar among institutions across the United States, and if not, could differences be explained by patient age, polyp size, and/or CRC rate. Nine academic institutions contributed data from three pathologists who had signed out at least 100 colorectal adenomatous polyps each from 2018 to 2019 taken from patients undergoing screening colonoscopy. For each case, we recorded patient age and sex, polyp size and location, concurrent CRC, and presence or absence of HGD and villous features. A total of 2700 polyps from 1886 patients (mean age: 61 years) were collected. One hundred twenty-four (5 %) of the 2700 polyps had advanced histology, including 35 (1 %) with HGD and 101 (4 %) with villous features. The diagnostic rate of advanced histology varied by institution from 1.7 % to 9.3 % (median: 4.3 %, standard deviation [SD]: 2.5 %). The rate of HGD ranged from 0 % to 3.3 % (median: 1 %, SD: 1.2 %), while the rate of villous architecture varied from 1 % to 8 % (median: 3.7 %, SD: 2.5 %). In a multivariate analysis, the factor most strongly associated with advanced histology was polyp size >1 cm with an odds ratio (OR) of 31.82 (95 % confidence interval [CI]: 20.52-50.25, p < 0.05). Inter-institutional differences in the rate of polyps >1 cm likely explain some of the diagnostic variance, but pathologic subjectivity may be another contributing factor.

Overcoming retinoic acid resistance in HER2-enriched breast cancers: role of MYC.

HER2-enriched (HER2+) breast cancers express high levels of the growth-promoting HER2 protein. Although these cancers are treated with the HER2-targeted drug, trastuzumab, resistance to treatment is common. Retinoic acid (RA) is an anti-cancer agent that has been successfully used for the treatment of leukemia and holds promise for the treatment of solid cancers, including breast cancer. The HER2 gene is frequently co-amplified with RARA, a key determinant of RA sensitivity in breast cancers. It seems surprising, therefore, that HER2+ breast cancers are refractory to RA treatment. Here, we show that MYC mediates RA resistance by suppressing the expression of cellular retinoic acid binding protein 2 (CRABP2), resulting in RARα inactivation. CRABP2 is an intracellular RA transporter that delivers RA to the nuclear receptor RARα for its activation. Our results indicate that response to RA is enhanced by MYC depletion in HER2+ breast cancer cells and that RA treatment enhances trastuzumab responsiveness. Our findings support the use of RA and trastuzumab for the treatment of subsets of patients with breast cancers that are HER2-RARα co-amplified and have low levels of MYC.

COVID-19 Vaccination Strategies in the Endemic Period: Lessons from Influenza.

Coronavirus disease 2019 (COVID-19) is a highly contagious zoonotic respiratory disease with many similarities to influenza. Effective vaccines are available for both; however, rapid viral evolution and waning immunity make them virtually impossible to eradicate with vaccines. Thus, the practical goal of vaccination is to reduce the incidence of serious illnesses and death. Three years after the introduction of COVID-19 vaccines, the optimal vaccination strategy in the endemic period remains elusive, and health authorities worldwide have begun to adopt various approaches. Herein, we propose a COVID-19 vaccination strategy based on the data available until early 2024 and discuss aspects that require further clarification for better decision making. Drawing from comparisons between COVID-19 and influenza vaccination strategies, our proposed COVID-19 vaccination strategy prioritizes high-risk groups, emphasizes seasonal administration aligned with influenza vaccination campaigns, and advocates the co-administration with influenza vaccines to increase coverage.

Crystalline Hepatopathy Associated With Bietti Crystalline Dystrophy: A Striking Manifestation of Disordered Fatty Acid Metabolism.

Bietti crystalline dystrophy (BCD) is a rare heritable retinal disease characterized by crystal deposition primarily in the retina. It is associated with atrophy of the retinal pigment epithelium (RPE) and is caused by variants in CYP4V2, which encodes a cytochrome P450 hemethiolate protein superfamily member. CYP4V2 is involved in the selective hydrolysis of saturated medium chain fatty acids, and patients with BCD demonstrate abnormalities in fatty acid metabolism, including abnormal lipid profiles and the accumulation of the pathogenic crystals within the RPE, which leads to the visual pathologies characteristic of BCD. However, the precise identity of the crystals is currently unknown, and BCD has no established extraocular manifestations. Here, we report granulomatous hepatitis associated with abundant diffuse crystalline clefts in the hepatic parenchyma in 3 patients with retinal dystrophy and dyslipidemia: 2 with pathogenic CYP4V2 variants and 1 patient with clinical ophthalmologic findings suggestive of BCD but without available genetic testing. The unique and striking histologic features unifying the liver biopsies in all 3 patients strongly support a process related to abnormal fatty acid metabolism underlying the genetic disease of BCD, expanding the spectrum of BCD and shedding light on the importance of CYP4V2 in systemic fatty acid metabolism.

Executive Summary of 2023 International Conference of the Korean Dementia Association (IC-KDA 2023): A Report From the Academic Committee of the Korean Dementia Association.

The Korean Dementia Association (KDA) has been organizing biennial international academic conferences since 2019, with the International Conference of the KDA (IC-KDA) 2023 held in Busan under the theme 'Beyond Boundaries: Advancing Global Dementia Solutions.' The conference comprised 6 scientific sessions, 3 plenary lectures, and 4 luncheon symposiums, drawing 804 participants from 35 countries. Notably, a Korea-Taiwan Joint Symposium addressed insights into Alzheimer's disease (AD). Plenary lectures by renowned scholars explored topics such as microbiome-related AD pathogenesis, social cognition in neurodegenerative diseases, and genetic frontotemporal dementia (FTD). On the first day, specific presentations covered subjects like the gut-brain axis and neuroinflammation in dementia, blood-based biomarkers in AD, and updates in AD therapeutics. The second day's presentations addressed recent issues in clinical neuropsychology, FTD cohort studies, and the pathogenesis of non-AD dementia. The Academic Committee of the KDA compiles lecture summaries to provide comprehensive understanding of the advanced dementia knowledge presented at IC-KDA 2023.

An exploratory study on spatiotemporal clustering of suicide in Korean adolescents.

BACKGROUND: Adolescent suicides are more likely to form clusters than those of other age groups. However, the definition of a cluster in the space-time dimension has not been established, neither are the factors contributing to it well known. Therefore, this study aimed to identify space-time clusters in adolescent suicides in Korea and to examine the differences between clustered and non-clustered cases using novel statistical methods. METHODS: From 2016 to 2020, the dates and locations, including specific addresses from which the latitude and longitude of all student suicides (aged 9-18 years) in Korea were obtained through student suicide reports. Sociodemographic characteristics of the adolescents who died by suicide were collected, and the individual characteristics of each student who died by suicide were reported by teachers using the Strengths and Difficulties Questionnaire (SDQ). Density-Based Spatial Clustering of Applications with Noise (DBSCAN) analysis was used to assess the clustering of suicides. RESULTS: We identified 23 clusters through the data analysis of 652 adolescent suicides using DBSCAN. By comparing the size of each cluster, we identified 63 (9.7%) spatiotemporally clustered suicides among adolescents, and the temporal range of these clusters was 7-59 days. The suicide cluster group had a lower economic status than the non-clustered group. There were no significant differences in other characteristics between the two groups. CONCLUSION: This study has defined the space-time cluster of suicides using a novel statistical method. Our findings suggest that when an adolescent suicide occurs, close monitoring and intervention for approximately 2 months are needed to prevent subsequent suicides. Future research using DBSCAN needs to involve a larger sample of adolescents from various countries to further corroborate these findings.

DNA flow cytometry for detection of genomic instability as a cancer precursor in the gastrointestinal tract.

One of the earliest applications of flow cytometry was the measurement of DNA content in cells. This method is based on the ability to stain DNA in a stoichiometric manner (i.e., the amount of stain is directly proportional to the amount of DNA within the cell). For more than 40years, a number of studies have consistently demonstrated the utility of DNA flow cytometry as a potential diagnostic and/or prognostic tool in patients with most epithelial tumors, including pre-invasive lesions (such as dysplasia) in the gastrointestinal tract. However, its availability as a clinical test has been limited to few medical centers due to the requirement for fresh tissue in earlier studies and perceived technical demands. However, more recent studies have successfully utilized formalin-fixed paraffin-embedded (FFPE) tissue to generate high-quality DNA content histograms, demonstrating the feasibility of this methodology. This review summarizes step-by-step methods on how to perform DNA flow cytometry using FFPE tissue and analyze DNA content histograms based on the published consensus guidelines in order to assist in the diagnosis and/or risk stratification of many different epithelial tumors, with particular emphasis on dysplasia associated with Barrett's esophagus and inflammatory bowel disease.

CRISPR-based editing strategies to rectify EYA1 complex genomic rearrangement linked to haploinsufficiency.

Pathogenic structure variations (SVs) are associated with various types of cancer and rare genetic diseases. Recent studies have used Cas9 nuclease with paired guide RNAs (gRNAs) to generate targeted chromosomal rearrangements, focusing on producing fusion proteins that cause cancer, whereas research on precision genome editing for rectifying SVs is limited. In this study, we identified a novel complex genomic rearrangement (CGR), specifically an EYA1 inversion with a deletion, implicated in branchio-oto-renal/branchio-oto syndrome. To address this, two CRISPR-based approaches were tested. First, we used Cas9 nuclease and paired gRNAs tailored to the patient's genome. The dual CRISPR-Cas9 system induced efficient correction of paracentric inversion in patient-derived fibroblast, and effectively restored the expression of EYA1 mRNA and protein, along with its transcriptional activity required to regulate the target gene expression. Additionally, we used CRISPR activation (CRISPRa), which leads to the upregulation of EYA1 mRNA expression in patient-derived fibroblasts. Moreover, CRISPRa significantly improved EYA1 protein expression and transcriptional activity essential for target gene expression. This suggests that CRISPRa-based gene therapies could offer substantial translational potential for approximately 70% of disease-causing EYA1 variants responsible for haploinsufficiency. Our findings demonstrate the potential of CRISPR-guided genome editing for correcting SVs, including those with EYA1 CGR linked to haploinsufficiency.

Drawing Guideline for JKMS Manuscripts (06): Scatter Plot.

The appropriate plot effectively conveys the author's conclusions to the readers. Journal of Korean Medical Science is providing a series of guidelines to show you how to make consistent and excellent plots more easily. In this article, we introduce scatter plots and more.

Interim Estimates of 2023-2024 Seasonal Influenza Vaccine Effectiveness Among Adults in Korea.

In the 2023-2024 season, the influenza epidemic in South Korea peaked earlier than in recent years. In this study, we aimed to estimate the interim vaccine effectiveness (VE) of the influenza vaccination to prevent influenza during the early season. From November 1, 2023, to December 31, 2023, we enrolled 2,632 subjects with influenza-like illness from eight hospitals participating in hospital-based influenza morbidity and mortality surveillance. A retrospective test-negative case-control study was conducted to estimate the VE. The results showed an adjusted VE of 22.5% (95% confidence interval [CI], 6.6 to 35.8) for the total population. The adjusted VE was 22.3% (95% CI, 6.1 to 35.7) for influenza A and 9.4% (95% CI, -51.3 to 45.7) for influenza A/H1N1. Full results of the analysis will be reported.