Background: Colorectal carcinomas (CRCs) with caudal-type homeobox 2 (CDX2) loss are recognized to pursue an aggressive behavior but tend to be accompanied by a high density of tumor-infiltrating lymphocytes (TILs). However, little is known about whether there is an interplay between CDX2 loss and TIL density in the survival of patients with CRC. Methods: Stage III CRC tissues were assessed for CDX2 loss using immunohistochemistry and analyzed for their densities of CD8 TILs in both intraepithelial (iTILs) and stromal areas using a machine learning-based analytic method. Results: CDX2 loss was significantly associated with a higher density of CD8 TILs in both intraepithelial and stromal areas. Both CDX2 loss and a high CD8 iTIL density were found to be prognostic parameters and showed hazard ratios of 2.314 (1.050–5.100) and 0.378 (0.175–0.817), respectively, for cancer-specific survival. A subset of CRCs with retained CDX2 expression and a high density of CD8 iTILs showed the best clinical outcome (hazard ratio of 0.138 [0.023–0.826]), whereas a subset with CDX2 loss and a high density of CD8 iTILs exhibited the worst clinical outcome (15.781 [3.939–63.230]). Conclusions Altogether, a high density of CD8 iTILs did not make a difference in the survival of patients with CRC with CDX2 loss. The combination of CDX2 expression and intraepithelial CD8 TIL density was an independent prognostic marker in adjuvant chemotherapy-treated patients with stage III CRC.

Purpose: Methacholine bronchial provocation tests (MBPTs) are commonly used to assess airway hyperresponsiveness, but some patients show no significant response. This study aimed to compare the clinical characteristics of asthmatic patients based on their sensitivity to MBPTs. Methods: We conducted a retrospective cross-sectional study involving adult asthmatic patients from 6 university hospitals in South Korea. Patients were categorized into 2 groups: those with MBPT sensitivity (the provocative concentration of methacholine that leads to a 20% reduction in forced expiratory volume in 1 second [PC20]≤ 16 mg/mL) and those with lower sensitivity (PC 20 > 16 mg/mL). Clinical characteristics were compared between the 2 groups. Results: Among 346 patients, 213 had PC 20 ≤ 16 mg/mL and 133 had PC 20 > 16 mg/mL. The PC20> 16 mg/mL group had a higher prevalence of late-onset asthma (P= 0.024) and obesity (P= 0.045). While no significant differences in immunoglobulin E (≥ 200 IU/mL) were found, the PC 20 ≤ 16 mg/mL group had greater T2-high inflammation, such as elevated eosinophil counts and fractional exhaled nitric oxide (P< 0.001 and P= 0.004, respectively). Asthma exacerbations requiring emergency visits or hospitalizations were more frequent in the PC 20 > 16 mg/mL group, despite a lower proportion of patients on higher-step treatments according to Global Initiative for Asthma guidelines. Conclusion Asthmatic patients with PC 20 > 16 mg/mL tend to present with late-onset asthma, less T2-high inflammation, and higher rates of asthma exacerbations. Further studies are needed to clarify the clinical features of asthma patients with PC 20 > 16 mg/mL and assess the long-term significance of these findings.

Previous studies have shown that testosterone activates the GPRC6A-Duox1 axis, resulting in the production of H 2O 2 which leads to the apoptosis of keratinocytes and ultimately hair loss. Here, we elucidated a molecular mechanism by which the non-genomic action of testosterone regulates cellular redox status in androgenetic alopecia (AGA). Building upon this molecular understanding, we conducted a high-throughput screening assay of Nox inhibitors from a natural compounds library. This screening identified diterpenoid compounds, specifically Tanshinone I, Tanshinone IIA, Tanshinone IIB, and Cryptotanshinone, derived from Salviae Miltiorrhizae Radix. The IC50 values for Nox isozymes were found to be 2.6-12.9 μM for Tanshinone I, 1.9-7.2 μM for Tanshinone IIA, 5.2-11.9 μM for Tanshinone IIB, and 2.1-7.9 μM for Cryptotanshinone. Furthermore, 3D computational docking analysis confirmed the structural basis by which Tanshinone compounds inhibit Nox activity. These compounds were observed to substitute for NADPH at the π-π bond site between NADPH and FAD, leading to the suppression of Nox activity. Notably, Tanshinone I and Tanshinone IIA effectively inhibited Nox activity heightened by testosterone, consequently reducing the production of intracellular H2O2 and preventing cell apoptosis. In an animal study involving the application of testosterone to the back skin of 8-week-old C57BL/6J mice to inhibit hair growth, subsequent treatment with Tanshinone I or Tanshinone IIA alongside testosterone resulted in a substantial increase in hair follicle length compared to testosterone treatment alone. These findings underscore the potential efficacy of Tanshinone I and Tanshinone IIA as therapeutic agents for AGA by inhibiting Nox activity.

Background: Severe fever with thrombocytopenia syndrome virus (SFTSV) is a lethal threat.Increasing Severe fever with thrombocytopenia syndrome (SFTS) risk in Asia and the United States stems from the spread of natural host, Haemaphysalis longicornis. Rapid and accurate SFTSV molecular diagnosis is crucial for treatment decisions, reducing fatality risk. Methods: Blood samples from 17 suspected SFTS patients at Chuncheon Sacred Heart Hospital (September-December 2022) were collected. SFTSV was diagnosed using two reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assays from Gangwon Institute of Health and Environment (RT-qPCR/GIHE) and Asan Medical Center (RT-qPCR/AMC). To address RT-qPCR disparities, amplicon-based MinION sequencing traced SFTSV genomic sequences in clinical samples. Results: In two samples (N39 and N50), SFTSV was detected in both RT-qPCR/GIHE and RTqPCR/AMC. Among 11 samples, RT-qPCR/AMC exclusively detected SFTSV. In four samples, both assays yielded negative results. Amplicon-based MinION sequencing enabled nearly whole-genome sequencing of SFTSV in samples N39 and N50. Among 11 discordant samples, five contained significant SFTSV reads, aligning with the RT-qPCR/AMC findings. However, another six samples showed insufficient viral reads in accordance with the negativity observed in RT-qPCR/GIHE. The phylogenetic pattern of SFTSV demonstrated N39 formed a genetic lineage with genotype A in all segments. SFTSV N50 grouped with the B-1 sub-genotype for L segment and B-2 sub-genotype for the M and S segments, indicating genetic reassortment. Conclusion The study demonstrates the robust sensitivity of amplicon-based MinION sequencing for the direct detection of SFTSV in clinical samples containing ultralow copies of viral genomes. Next-generation sequencing holds potential in resolving SFTSV diagnosis discrepancies, enhancing understanding of diagnostic capacity, and risk assessment for emerging SFTSV.

Background: Severe fever with thrombocytopenia syndrome virus (SFTSV) is a lethal threat.Increasing Severe fever with thrombocytopenia syndrome (SFTS) risk in Asia and the United States stems from the spread of natural host, Haemaphysalis longicornis. Rapid and accurate SFTSV molecular diagnosis is crucial for treatment decisions, reducing fatality risk. Methods: Blood samples from 17 suspected SFTS patients at Chuncheon Sacred Heart Hospital (September-December 2022) were collected. SFTSV was diagnosed using two reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assays from Gangwon Institute of Health and Environment (RT-qPCR/GIHE) and Asan Medical Center (RT-qPCR/AMC). To address RT-qPCR disparities, amplicon-based MinION sequencing traced SFTSV genomic sequences in clinical samples. Results: In two samples (N39 and N50), SFTSV was detected in both RT-qPCR/GIHE and RTqPCR/AMC. Among 11 samples, RT-qPCR/AMC exclusively detected SFTSV. In four samples, both assays yielded negative results. Amplicon-based MinION sequencing enabled nearly whole-genome sequencing of SFTSV in samples N39 and N50. Among 11 discordant samples, five contained significant SFTSV reads, aligning with the RT-qPCR/AMC findings. However, another six samples showed insufficient viral reads in accordance with the negativity observed in RT-qPCR/GIHE. The phylogenetic pattern of SFTSV demonstrated N39 formed a genetic lineage with genotype A in all segments. SFTSV N50 grouped with the B-1 sub-genotype for L segment and B-2 sub-genotype for the M and S segments, indicating genetic reassortment. Conclusion The study demonstrates the robust sensitivity of amplicon-based MinION sequencing for the direct detection of SFTSV in clinical samples containing ultralow copies of viral genomes. Next-generation sequencing holds potential in resolving SFTSV diagnosis discrepancies, enhancing understanding of diagnostic capacity, and risk assessment for emerging SFTSV.

Background: and Purpose The National Brain Biobank of Korea (NBBK) is a brain bank consortium supported by the Korea Disease Control and Prevention Agency and the Korea National Institute of Health, and was launched in 2015 to support research into neurodegenerative disease dementia (NDD). This study aimed to introduce the NBBK and describes clinicopathological correlations based on analyses of data collected from the NBBK. Methods: Four hospital-based brain banks have been established in South Korea: Samsung Medical Center Brain Bank (SMCBB), Seoul National University Hospital Brain Bank (SNUHBB), Pusan National University Hospital Brain Bank (PNUHBB), and Myongji Hospital Brain Bank (MJHBB). Clinical and pathological data were collected from these brain banks using standardized protocols. The prevalence rates of clinical and pathological diagnoses were analyzed in order to characterize the clinicopathological correlations. Results: Between August 2016 and December 2023, 185 brain specimens were collected and pathologically evaluated (SNUHBB: 117; PNUHBB: 27; SMCBB: 34; MJHBB: 7). The age at consent was 70.8±12.6 years, and the age at autopsy was 71.7±12.4 years. The four-most-common clinical diagnoses were Alzheimer’s disease (AD) dementia (20.0%), idiopathic Parkinson’s disease (15.1%), unspecified dementia (11.9%), and cognitively unimpaired (CU) (11.4%).Most cases of unspecified dementia had a pathological diagnosis of central nervous system (CNS) vasculopathy (31.8%) or AD (31.8%). Remarkably, only 14.2% of CU cases had normal pathological findings. The three-most-common pathological diagnoses were AD (26.5%), CNS vasculopathy (14.1%), and Lewy body disease (13.5%). Conclusions These clinical and neuropathological findings provide a deeper understanding of the mechanisms underlying NDD in South Korea.

Purpose: This study evaluated the postoperative quality of life (QoL) after various types of gastrectomy for gastric cancer. Materials and Methods: A multicenter prospective observational study was conducted in Korea using the Korean Quality of Life in Stomach Cancer Patients Study (KOQUSS)-40, a new QoL assessment tool focusing on postgastrectomy syndrome. Overall, 496 patients with gastric cancer were enrolled, and QoL was assessed at 5 time points: preoperatively and at 1, 3, 6, and 12 months after surgery. Results: Distal gastrectomy (DG) and pylorus-preserving gastrectomy (PPG) showed significantly better outcomes than total gastrectomy (TG) and proximal gastrectomy (PG) with regard to total score, indigestion, and dysphagia. DG, PPG, and TG also showed significantly better outcomes than PG in terms of dumping syndrome and worry about cancer. Postoperative QoL did not differ significantly according to anastomosis type in DG, except for Billroth I anastomosis, which achieved better bowel habit change scores than the others. No domains differed significantly when comparing double tract reconstruction and esophagogastrostomy after PG. The total QoL score correlated significantly with postoperative body weight loss (more than 10%) and extent of resection (P<0.05 for both).Reflux as assessed by KOQUSS-40 did not correlate significantly with reflux observed on gastroscopy 1 year postoperatively (P=0.064). Conclusions Our prospective observation using KOQUSS-40 revealed that DG and PPG lead to better QoL than TG and PG. Further study is needed to compare postoperative QoL according to anastomosis type in DG and PG.