Intraflagellar transport (IFT) particles, a multi-protein apparatus composed of complex A and B, are known to be involved in homeostasis of flagella formation. IFT particles have recently become an interesting topic in Giardia lamblia, which has 4 pairs of flagella. In this experiment, we examined the function of giardial IFT components. When 7 components (IFT121, 140, 20, 46, 52, 81, and 88) of IFT were expressed in Giardia trophozoites as a tagged form with mNeonGreen, all of them were found in both flagella pores and cytoplasmic axonemes. In addition, motor proteins for IFT particles (kinesin-13 and kinesin-2b), were localized to a median body and cytoplasmic flagella, respectively. The CRISPRi-mediated knockdown of IFT88 significantly affected the lengths of all 4 flagella compared to the control cells, Giardia expressing dead Cas9 using control guide RNA. Decreased expression of kinesin-2b also resulted in shortening of flagella, excluding the ventral flagella. Live Giardia cells expressing IFT88-mNeonGreen clearly demonstrated fluorescence in flagella pores and cytoplasmic axonemes. These results on IFT88 and kinesin-2b indicate that IFT complex plays a role in maintenance of G. lamblia flagella.

Gastrointestinal stromal tumors (GISTs) are rare mesenchymal neoplasms that mainly occur in the stomach and small intestine; those arising in the esophagus are rarer. A 54-year-old woman was referred to our hospital with a one-month history of dysphagia. Esophagogastroduodenoscopy (EGD), performed approximately five months earlier, had not revealed any specific findings. However, an EGD performed in our hospital showed the presence of a round, protruding lesion (approximately 40×30 mm in size), with a normal overlying mucosal surface, 35–39 cm from the upper incisor. Chest computed tomography (CT) revealed a large esophageal mass. Enucleation was performed on the esophageal mass, and a GIST was diagnosed using immunochemical staining. Imatinib mesylate administration was initiated two months postoperatively. The patient was stable, without any evident recurrence in the 8-month postoperative follow-up EGD and chest CT examinations. Therefore, physicians should consider that patients with worsening dysphagia may have an underlying organic condition, such as an acute increase in size of an esophageal GIST, even if recent examinations were unremarkable.

Fine particulate matter (FPM) is a major component of air pollution and has emerged as a significant global health concern owing to its adverse health effects. Previous studies have investigated the correlation between bone health and FPM through cohort or review studies. However, the effects of FPM exposure on bone health are poorly understood. This study aimed to investigate the effects of FPM on bone health and elucidate these effects in vitro and in vivo using mice. Micro-CT analysis in vivo revealed FPM exposure decreased bone mineral density, trabecular bone volume/total volume ratio, and trabecular number in the femurs of mice, while increasing trabecular separation. Histological analysis showed that the FPM-treated group had a reduced trabecular area and an increased number of osteoclasts in the bone tissue. Moreover, in vitro studies revealed that low concentrations of FPM significantly enhanced osteoclast differentiation. These findings further support the notion that short-term FPM exposure negatively impacts bone health, providing a foundation for further research on this topic.

Background: High-resolution chest computed tomography (CT) is a crucial assessment tool for diagnosing Birt-Hogg-Dubé (BHD) syndrome. This study aimed to analyze differences of lung cysts between BHD and other cystic lung diseases. Methods: From January 2020 to December 2022, patients with multiple lung cysts who underwent chest CT at Gangnam Severance Hospital were included. Results: Over a 3-year period (from January 2020 to December 2022), out of 52,823 patients who underwent a chest CT scan, 301 (0.6%) patients with multiple lung cysts were enrolled in this study. Of enrolled patients, 24 (8.0%) were diagnosed with BHD. In patients with BHD, 95.8% exhibited bilateral cysts, and 83.3% showed basal predominance. The cysts’ maximal diameter averaged 32.1 mm (interquartile range, 26.5 to 43.5). Additionally, 95.8% of patients with BHD had diverse cyst sizes and morphologies. Multivariate logistic regression analysis revealed that bilateral cysts (odds ratio [OR], 12.393; 95% confidence interval [CI], 1.613 to 274.682; p=0.038), basal predominance (OR, 8.511; 95% CI, 2.252 to 39.392; p=0.002), maximum diameter (OR, 1.053; 95% CI, 1.009 to 1.108; p=0.032), and diversity of morphology (OR, 19.513; 95% CI, 2.833 to 398.119; p=0.010) were significant factors associated with BHD diagnosis. A multivariate prediction model for BHD diagnosis demonstrated a sensitivity of 95.83%, a specificity of 81.22%, and an area under the receiver operating characteristic curve of 0.951 (95% CI, 0.914 to 0.987). Conclusion Distinguishing features of lung cysts from other cystic lung diseases include bilateral cysts, basal dominance, large size, and irregular shape.

Background: The development of frailty at hospital discharge affects the clinical outcomes in severe coronavirus disease 2019 (COVID-19) survivors who had no frailty before hospitalization. We aimed to describe the prevalence of new frailty using the clinical frailty scale (CFS) and evaluate its associated factors in patients with severe COVID-19 without pre-existing frailty before hospitalization. Methods: We performed a secondary analysis of clinical data from a nationwide retrospective cohort collected from 22 hospitals between January 1, 2020 and August 31, 2021. The patients were at least 19 years old and survived until discharge after admission to the intensive care unit (ICU) because of severe COVID-19. Development of new frailty was defined as a CFS score ≥5 at hospital discharge. Results: Among 669 severe COVID-19 survivors without pre-existing frailty admitted to the ICU, the mean age was 65.2±12.8 years, 62.5% were male, and 50.2% received mechanical ventilation (MV). The mean CFS score at admission was 2.4±0.9, and new frailty developed in 27.8% (186/483). In multivariate analysis, older age, cardiovascular disease, CFS score of 3–4 before hospitalization, increased C-reactive protein level, longer duration of corticosteroid treatment, and use of MV and extracorporeal membrane oxygenation were identified as factors associated with new-onset frailty. Conclusion Our study suggests that new frailty is not uncommon and is associated with diverse factors in survivors of severe COVID-19 without pre-existing frailty.

Background: Kelch-like ECH-associated protein 1 (KEAP1)–nuclear factor erythroid- 2-related factor 2 (NRF2) pathway is a major regulator protecting cells from oxidative and metabolic stress. Studies have revealed that this pathway is involved in mediating resistance to cytotoxic chemotherapy and immunotherapy; however, its implications in oncogene-addicted tumors are largely unknown. This study aimed to elucidate whether this pathway could be a potential therapeutic target for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer. Methods: We measured the baseline expression of NRF2 using EGFR-mutant parental cells and acquired gefitinib resistant cells. We investigated whether NRF2 inhibition affected cell death in vitro and tumor growth in vivo using a xenograft mouse model, and compared the transcriptional changes before and after NRF2 inhibition. Results: Baseline NRF2 expression was enhanced in PC9 and PC9 with gefitinib resistance (PC9/GR) cells than in other cell lines, with a more prominent expression in PC9/ GR. The NRF2 inhibitor induced NRF2 downregulation and cell death in a dose-dependent manner. Cotreatment with an NRF2 inhibitor enhanced osimertinib-induced cell death in vitro, and potentiated tumor growth inhibition in a PC9/GR xenograft model. Finally, RNA sequencing revealed that NRF2 inhibition resulted in the altered expression of multiple genes involved in various signaling pathways. Conclusion We identified that NRF2 inhibition enhanced cell death and inhibited tumor growth in tyrosine kinase inhibitor (TKI)-resistant lung cancer with EGFR-mutation. Thus, NRF2 modulation may be a novel therapeutic strategy to overcome the resistance to EGFR-TKIs.

Purpose: This study evaluated the educational impact of an artificial intelligence (AI)–based decision support system for breast ultrasonography (US) on medical professionals not specialized in breast imaging. Methods: In this multi-case, multi-reader study, educational materials, including American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) descriptors, were provided alongside corresponding AI results during training. The AI system presented results in the form of AIheatmaps, AI scores, and AI-provided BI-RADS assessment categories. Forty-two readers evaluated the test set in three sessions: the first session (S1) occurred before the educational intervention, the second session (S2) followed education without AI assistance, and the third session (S3) took place after education with AI assistance. The area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and overall performance, were compared between the sessions. Results: The mean sensitivity increased from 66.5% (95% confidence interval [CI], 59.2% to 73.7%) to 88.7% (95% CI, 84.1% to 93.3%), with a statistically significant difference (P<0.001), and the AUC non-significantly increased from 0.664 (95% CI, 0.606 to 0.723) to 0.684 (95% CI, 0.620 to 0.748) (P=0.300). Both measures were higher in S2 than in S1. The AI-achieved AUC was comparable to that of the expert reader (0.747 [95% CI, 0.640 to 0.855] vs. 0.803 [95% CI, 0.706 to 0.900], P=0.217). Additionally, with AI assistance, the mean AUC for inexperienced readers was not significantly different from that of the expert reader (0.745 [95% CI, 0.660 to 0.830] vs. 0.803 [95% CI, 0.706 to 0.900], P=0.120). Conclusion The mean AUC and sensitivity improved after incorporating AI into breast US education and interpretation. AI systems with high-level performance for breast US can potentially be used as educational tools in the interpretation of breast US images.

Background: s/Aims: Hepatocellular carcinoma (HCC) is the sixth most common cancer and second leading cause of cancer-related deaths in South Korea. This study evaluated the characteristics of Korean patients newly diagnosed with HCC in 2016-2018. Methods: Data from the Korean Primary Liver Cancer Registry (KPLCR), a representative database of patients newly diagnosed with HCC in South Korea, were analyzed. This study investigated 4,462 patients with HCC registered in the KPLCR in 2016-2018. Results: The median patient age was 63 years (interquartile range, 55-72). 79.7% of patients were male. Hepatitis B infection was the most common underlying liver disease (54.5%). The Barcelona Clinic Liver Cancer (BCLC) staging system classified patients as follows: stage 0 (14.9%), A (28.8%), B (7.5%), C (39.0%), and D (9.8%). The median overall survival was 3.72 years (95% confidence interval, 3.47-4.14), with 1-, 3-, and 5-year overall survival rates of 71.3%, 54.1%, and 44.3%, respectively. In 2016-2018, there was a significant shift toward BCLC stage 0-A and Child-Turcotte-Pugh liver function class A (P<0.05), although survival rates did not differ by diagnosis year. In the treatment group (n=4,389), the most common initial treatments were transarterial therapy (31.7%), surgical resection (24.9%), best supportive care (18.9%), and local ablation therapy (10.5%). Conclusions Between 2016 and 2018, HCC tended to be diagnosed at earlier stages, with better liver function in later years. However, since approximately half of the patients remained diagnosed at an advanced stage, more rigorous and optimized HCC screening strategies should be implemented.

Background/Aims: Fexuprazan, a novel potassium-competitive acid blocker, was developed for treating acid-related disorders. Pharmacokinetic and pharmacodynamic properties of fexuprazan, unlike those of proton pump inhibitors, are independent of food effect. This study aims to evaluate differences in efficacy and safety of fexuprazan in patients with erosive esophagitis (EE) according to the timing of dosing. Methods: In this multicenter, open-label noninferiority study, patients who had typical reflux symptoms with endoscopically confirmed EE were randomized 1:1 to receive fexuprazan 40 mg daily 30 minutes before or after meal. Treatment was completed after 2 weeks or 4 weeks when healing was endoscopically confirmed. The primary endpoint was the proportion of patients with healed EE confirmed by endoscopy up to week 4. Safety endpoints included treatment-emergent adverse events (TEAEs). Results: In the prior-to-meal group (n = 89) and after-meal group (n = 86), 4-week EE healing rates were 98.77% and 100.00% (difference, 0.01%; 95% CI, –0.01% to 0.04%) and 2-week EE healing rates were 95.77% and 97.14% (difference, 0.01%; 95% CI, –0.05% to 0.07%), respectively. TEAEs were 9.78% and 8.70% in the prior-to-meal group and the after-meal group, respectively. Conclusions Non-inferiority analysis revealed that taking fexuprazan after meal was non-inferior to taking fexuprazan before meals in patients with EE. The frequency of adverse events was similar between the 2 study groups. The drug is safe and effective for healing EE regardless of the timing of dosing.

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.