In light of the burgeoning successes of cancer immunotherapy, glioblastoma (GBM) remains refractory due to an immunosuppressive microenvironment originating from its molecular heterogeneity. Thus, identifying promising therapeutic targets for treating GBM and discovering methodologies to effectively regulate them is still a tremendous challenge. Here we describe photodynamic protein tyrosine phosphatase 1B (PTP1B) proteolysis mediated by a proteolysis-targeting chimera (PROTAC) nanoassembly. The PTP1B-targeting PROTAC is conjugated with a photosensitizer via a cathepsin B (Cat B)-cleavable peptide, which spontaneously forms nanoassemblies due to intermolecular π-π stacking interactions. In GBM models, PROTAC nanoassemblies significantly accumulate in the tumor region across the disrupted blood-brain barrier (BBB), triggering a burst release of the photosensitizer and active PROTAC by Cat B-mediated enzymatic cleavage. Upon laser irradiation, photodynamic therapy (PDT) synergizes with PROTAC-mediated PTP1B proteolysis to induce potent immunogenic cell death (ICD) in tumor cells. Subsequently, persistent PTP1B degradation by nanoassemblies in Cat B-overexpressed intratumoral T cells downregulates exhaustion markers, reinvigorating their functionality. These sequential processes of photodynamic PTP1B proteolysis ultimately augment T cell-mediated antitumor immunity as well as protective immunity, completely eradicating the primary GBM and preventing its recurrence. Overall, our findings underscore the therapeutic potential of combining PDT with PROTAC activity for GBM immunotherapy.

Objective: To compare coronary artery dimension-adjusted subtended myocardial mass between patients with hypertrophic cardiomyopathy (HCM) and a normal population without detectable atherosclerosis, and between HCM patients with and without chest pain. Materials and Methods: Twenty-five patients with HCM but no detectable atherosclerosis on coronary computed tomography angiography (CCTA) were included in the study. This group comprised 14 patients with chest pain and 11 patients without chest pain. They were matched with 25 healthy participants based on sex, age, coronary dominance pattern, and body surface area. The minimal lumen area (MLA) and subtended myocardial volume (V sub) were assessed in the left main (LM), proximal left anterior descending (pLAD), proximal left circumflex (pLCx), and proximal right coronary (pRCA) arteries. Additionally, an index of the subtended myocardial mass adjusted for the MLA, calculated as V sub/MLA 2 , was determined. Results: MLA was significantly larger in patients with HCM compared to the control group in LM (20.93 ± 6.31 mm 2 vs.15.24 ± 3.90 mm 2 , P< 0.001), pLAD (14.28 ± 3.55 mm 2 vs. 11.36 ± 2.07 mm 2, P = 0.001), pLCx (10.94 ± 3.60 mm 2 vs. 9.15 ± 2.93 mm 2 , P = 0.045), and pRCA (13.41 ± 4.85 mm 2 vs. 11.22 ± 3.20 mm 2 , P = 0.018). Despite an increase in coronary luminal area, patients with HCM exhibited significantly higher V sub/MLA 2 compared to the control group in both the pLAD (403.56 ± 200.35 mm -1 vs. 241.70 ± 85.87 mm -1 , P < 0.001) and the pRCA (186.06 ± 95.07 mm -1 vs. 125.07 ± 70.18 mm -1 , P= 0.007). V sub/MLA 2 was significantly elevated in patients with chest pain compared to those without in the pLAD (473.75 ± 227.38 mm -1 vs. 314.24 ± 110.74 mm -1 , P = 0.018) and the pLCx (417.04 ± 182.65 mm -1 vs. 275.29 ± 112.97 mm -1 , P = 0.044). Conclusion CCTA-derived V sub/MLA 2 may more accurately reflect the balance between myocardial blood supply and demand, offering insights into the occurrence of demand angina in patients with HCM without obstructive coronary artery disease.

Radiofrequency ablation (RFA) is a minimally invasive treatment modality used as an alternative to surgery in patients with benign thyroid nodules, recurrent thyroid cancers (RTCs), and primary thyroid microcarcinomas. The Korean Society of Thyroid Radiology (KSThR) initially developed recommendations for the optimal use of RFA for thyroid tumors in 2009 and revised them in 2012 and 2017. As new meaningful evidence has accumulated since 2017 and in response to a growing global interest in the use of RFA for treating malignant thyroid lesions, the task force committee members of the KSThR decided to update the guidelines on the use of RFA for the management of RTCs based on a comprehensive analysis of current literature and expert consensus.

Objective: To assess the feasibility of ultrafast brain magnetic resonance imaging (MRI) in pediatric patients. Materials and Methods: We retrospectively reviewed 194 pediatric patients aged 0 to 19 years (median 10.2 years) who underwent both ultrafast and conventional brain MRI between May 2019 and August 2020. Ultrafast MRI sequences included T1 and T2-weighted images (T1WI and T2WI), fluid-attenuated inversion recovery (FLAIR), T2*-weighted image (T2*WI), and diffusion-weighted image (DWI). Qualitative image quality and lesion evaluations were conducted on 5-point Likert scales by two blinded radiologists, with quantitative assessment of lesion count and size on T1WI, T2WI, and FLAIR sequences for each protocol. Wilcoxon signed-rank tests and intraclass correlation coefficient (ICC) analyses were used for comparison. Results: The total scan times for equivalent image contrasts were 1 minute 44 seconds for ultrafast MRI and 15 minutes 30 seconds for conventional MRI. Overall, image quality was lower in ultrafast MRI than in conventional MRI, with mean quality scores ranging from 2.0 to 4.8 for ultrafast MRI and 4.8 to 5.0 for conventional MRI across sequences (P < 0.001 for T1WI, T2WI, FLAIR, and T2*WI for both readers; P = 0.018 [reader 1] and 0.031 [reader 2] for DWI). Lesion detection rates on ultrafast MRI relative to conventional MRI were as follows: T1WI, 97.1%; T2WI, 99.6%; FLAIR, 92.9%; T2*WI, 74.1%; and DWI, 100%. The ICC (95% confidence interval) for lesion size measurements between ultrafast and conventional MRI was as follows: T1WI, 0.998 (0.996–0.999); T2WI, 0.998 (0.997–0.999); and FLAIR, 0.99 (0.985–0.994). Conclusion Ultrafast MRI significantly reduces scan time and provides acceptable results, albeit with slightly lower image quality than conventional MRI, for evaluating intracranial abnormalities in pediatric patients.

Background/Aims: Adiponectin, a hormone primarily produced by adipocytes, typically shows an inverse relationship with body mass index (BMI). However, some studies have reported a positive correlation between the two. Thus, this study aimed to examine the relationship between adiponectin level and BMI in diabetic patients, focusing on the impact of past obesity on current adiponectin levels. Methods: We conducted an observational study analyzing data from 323 diabetic patients at Kyungpook National University Hospital. Based on past and current BMIs, participants were categorized into never-obese (nn, n = 106), previously obese (on, n = 43), and persistently obese (oo, n = 73) groups based on a BMI threshold of 25 kg/m2. Adiponectin level and BMI were key variables. Kaplan–Meier analysis assessed their impact on all-cause mortality up to August 2023, with survival differences based on adiponectin quartiles and follow-up starting from patient enrollment (2010–2015). Results: The analysis revealed a significant inverse correlation between adiponectin level and past maximum BMI. The on group exhibited approximately 10% lower adiponectin levels compared to the nn group. This association remained significant after adjusting for current BMI, age, and sex, highlighting the lasting influence of previous obesity on adiponectin levels. Furthermore, survival analysis indicated that patients in the lowest adiponectin quartile had reduced survival, with a statistically significant trend (p = 0.062). Conclusions Findings of this study suggest that lower adiponectin levels, potentially reflecting past obesity, are associated with decreased survival in diabetic patients, underscoring a critical role of adiponectin in long-term health outcomes.

Background/Aims: Krebs von den Lungen-6 (KL-6) is associated with prognosis in patients with COVID-19. However, there is limited data on the correlation between the prognosis of COVID-19 and varying KL-6 levels at different time points. We investigated the optimal cutoff values of the initial and peak serum KL-6 levels to predict mortality and evaluated their correlation with mortality. Methods: This retrospective cohort study collected data on serially collected serum KL-6 levels in patients hospitalized with COVID-19 between October 2020 and January 2022 at a single tertiary hospital in South Korea. The area under the receiver operating characteristic curve and Youden index were used to determine the cutoff points for the initial and peak KL-6 levels that best predicted 30-day mortality. The association between the initial and peak KL-6 values was assessed by univariate and multivariate logistic regression models. Results: A total of 349 patients were included in this study. The mean initial and peak KL-6 levels were significantly higher in the non-survivor group than in the survivor group. The initial and peak KL-6 values that best predicted 30-day mortality were 491.85 U/mL and 660.05 U/mL, respectively. An initial KL-6 level greater than 491.85 U/mL and a peak KL-6 level greater than 660.05 U/mL were significantly associated with 30-day mortality. Conclusions The initial and peak levels of KL-6 were significantly associated with 30-day mortality in hospitalized patients with COVID-19. These findings suggest that serially monitoring blood KL-6 levels could be a valuable prognostic indicator for COVID-19.

Objective: Extraction of the mandibular second molar (L7) and substitution by the mandibular third molar (L8) is an effective treatment option. This study aimed to evaluate spontaneously erupted L8 occlusion after L7 extraction, and identify the influencing factors. Methods: This study assessed 46 L8 from 28 patients using dental study models, panoramic radiographs, and lateral cephalograms obtained during L7 extraction (T1) and completion of L8 eruption (T2). At T2, samples were categorized as acceptable (A-group) or unacceptable (U-group) based on the American Board of Orthodontics index.L8 angulation and position, retromolar space, distance between the Xi point and mandibular first molar (L6), and Nolla stage were compared between the groups to identify the predictive factors for successful eruption. Results: At T2, 58.7% of L8 exhibited acceptable occlusion. Age at T1 was significantly higher in the U-group than that in the A-group. Angles ∠6-MnP and ∠8-MnP differed significantly between the groups at T2. Xi-L6 distance was considerably longer in the A-group than that in the U-group at T1 and T2. Younger age at extraction and Xi-L6 distance at T1 affected the acceptable occlusion. Conclusions Younger age at L7 extraction and adequate eruption space (Xi-L6 distance) appear to be the key factors for achieving acceptable L8 occlusion.

Background: Chronic pain significantly affects daily activities, mental health, and the interpersonal relationships of patients. Consequently, physicians use various treatments to manage pain. This study investigated the perceptions of treatment, accompanying symptoms, and other problems in patients with chronic pain. Methods: The authors enrolled patients with chronic pain from 19 university hospitals in South Korea. Data was collected on age, gender, diagnosis, disease duration, severity of pain, perception of pain treatment, and accompanying symptoms or problems using an anonymous survey comprising 19 questions. Results: In total, 833 patients with chronic pain completed the survey, and 257 (31.0%) and 537 (64.5%) patientsexpressed concerns about the potential adverse effects of medication and opioid addiction, respectively. Personalitychanges such as irritability or anger were the most frequent accompanying symptoms in 507 (63.8%) patients, followed by depression and sleep disturbance in 462 (58.1%) and 450 (54.5%) patients, respectively. Depression (P = 0.001) and anxiety (P = 0.029) were more common among women, whereas divorce (P = 0.016), family conflict (P < 0.001), unemployment (P < 0.001), suicide attempts (P < 0.001), and restrictions on economic activity (P < 0.001) were more common among men. The frequency of accompanying symptoms, except for suicidal ideation,was higher in the younger patients aged ≤ 40 years than in the older patients aged > 40 years. Conclusions Many patients with chronic pain had concerns about adverse effects or medication tolerance and experienced anxiety, depression, or sleep disturbances. The prevalence of accompanying problems varies according to age and gender.

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: 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.