Introduction:Low psoas muscle radiodensity (PMD) on computed tomography (CT) indicates impaired muscle quality and is widely used as an operational marker of myosteatosis in individuals with obesity. In this study, we aimed to develop and internally validate a clinically accessible prediction model for low PMD in adults with severe obesity. Methods:This retrospective study included 150 adults with severe obesity, defined as body mass index (BMI) ≥ 35 kg/m2, who underwent CT evaluation as candidates for metabolic and bariatric surgery at our university hospital between January 2019 and May 2025. PMD was quantified on CT, and low PMD was defined as the lowest quartile [cutoff: ≤40.8 Hounsfield units (HU)]. A prediction model incorporating age, BMI, serum albumin, and bioelectrical impedance analysis-derived phase angle (PhA) was developed. Model performance was assessed using discrimination and accuracy metrics, with internal validation by bootstrapping. Results:The mean age, BMI, and PMD were 37.0 ± 10.6 years, 40.30 ± 8.05 kg/m2, and 45.90 ± 8.76 HU, respectively. PhA provided incremental explanatory value for PMD (ΔR 2 = 0.048, p = 0.001). In multivariable logistic regression analysis, age and BMI were independently associated with low PMD, whereas albumin and PhA were not significantly associated with low PMD; however, their incremental contribution was assessed based on predictive performance. The integrated model demonstrated improved discrimination compared with the age-BMI model [area under the curve (AUC) = 0.841 vs. 0.829]. At an optimal cutoff of 0.38, the sensitivity was 67.5%, specificity was 85.5%, and optimism-corrected AUC was 0.821. Discussion:This clinically accessible model demonstrated good discrimination and high specificity, supporting clinical risk stratification in settings where CT is limited.

Evidence on whether alcohol consumption and drinking patterns contribute to the risk of primary malignant brain tumors remains limited. We examined associations of daily alcohol consumption, drinking frequency, and heavy episodic drinking with tumor incidence in a nationwide cohort. We analyzed data from the National Health Insurance Service-National Sample Cohort (version 2.2), including 240,948 adults aged ≥ 20 years who completed a general health screening between 2006 and 2008. Alcohol-related behaviors were assessed using standardized questionnaires. Incident primary malignant brain tumors were identified using code C71 and the special registration code V193. Hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards models adjusting for sociodemographic and lifestyle factors. Over a mean follow-up of 12 years, 209 incident malignant brain tumors occurred (7.2 per 100,000 person-years). Daily alcohol consumption and heavy episodic drinking were not associated with tumor risk. In contrast, drinking frequency showed a positive association: participants who drank almost daily had a higher risk (vs. non-drinkers) (HR, 2.61; 95% CI, 1.21-5.61; P-trend = 0.0347). Sensitivity analyses restricted to adults aged ≥ 40 years and excluding early cases (3- or 5-year latency) yielded similar results. No effect modification was observed. In this nationwide Korean cohort, near-daily drinking, rather than daily alcohol consumption or amount consumed per occasion, was associated with an elevated risk of primary malignant brain tumors. These findings suggest that drinking frequency may represent an independent dimension of alcohol exposure relevant to brain tumor risk.

Background/Objectives: Current data-driven dietary pattern methods have limitations in identifying disease-specific dietary structures. We developed network-derived dietary scores based on type 2 diabetes (T2D)-differential food co-consumption networks and examined their associations with incident T2D risk. Methods: Using the Korean Genome and Epidemiology Study-CArdioVascular disease Association Study (KoGES-CAVAS, n = 16,665), we constructed food co-consumption networks from cumulative average intakes stratified by incident T2D status. The network centrality scores from edges appearing exclusively in either T2D or non-T2D networks were used to generate a differential co-consumption network-derived (D_CCN) score, with higher scores indicating a greater alignment with diabetes-specific structures. CAVAS-derived scores were applied to the Health Examinee Study (KoGES-HEXA, n = 51,206) for cross-cohort validation. Incidence rate ratios (IRRs) were estimated using modified Poisson regression with robust error estimation. Results: During follow-up, 953 and 2190 new cases of T2D were identified in CAVAS and HEXA, respectively. Rice and vegetable dishes were primary hub foods in both networks, with rice showing exclusively negative correlations. Non-T2D networks were more complex, whereas T2D networks were simpler and centered on refined flour-based foods. The D_CCN score was associated with a higher T2D risk in CAVAS (IRR = 1.45, 95% CI: 1.21-1.74), and this association was validated in HEXA (IRR = 1.58, 95% CI: 1.40-1.78), with consistent dose-response relationships (both p-trend < 0.0001). Conclusions: Differential network analysis identified T2D-specific co-consumption structures, and the D_CCN score consistently predicted T2D risk across cohorts. This approach highlights the utility of network-based methods for capturing disease-relevant dietary structures beyond traditional approaches.

Cushing's disease (CD) is a rare but serious endocrine disorder caused by excessive cortisol secretion due to adrenocorticotropic hormone-secreting pituitary tumors. Despite recent developments in diagnostic criteria and treatment options, CD remains associated with substantial comorbidities and mortality. Early and accurate diagnosis is thus essential. Both the Korean Endocrine Society (KES) and Japan Endocrine Society (JES) guidelines are intended to standardize diagnostic approaches to CD, and they share common principles; however, notable differences exist, particularly in biochemical testing thresholds and imaging recommendations. This consensus statement integrates clinical evidence and expert practice from both the KES and JES to establish harmonized recommendations for biochemical evaluation, imaging, and differential testing. This unified framework is intended to enhance diagnostic precision and improve clinical outcomes across East Asian populations.

Abstract PARP7 (TIPARP, TCDD-induced poly[ADP-ribose] polymerase) is a stress-inducible mono-ADP-ribosyltransferase frequently overexpressed across multiple cancer types. Elevated PARP7 expression has been implicated in tumor progression, immune evasion, and the establishment of an immunosuppressive tumor microenvironment (TME). Mechanistically, in cancer cells, PARP7 negatively regulates type I interferon (IFN) signaling by mono-ADP-ribosylating TBK1, thereby suppressing nucleic acid sensing and dampening antitumor immune activation within the TME. Pharmacological inhibition of PARP7 restores IFN signaling and potentiates immune-mediated antitumor responses. In addition to immune activation, PARP7 inhibition exerts tumor-intrinsic antitumor effects through multiple cellular mechanisms, culminating in direct tumor cell growth inhibition. Collectively, these findings suggest that targeting PARP7 may offer superior therapeutic potential compared with current immuno-oncology (IO) approaches by coupling immune activation with tumor-intrinsic control. In this study, we identified a novel small-molecule PARP7 inhibitor, referred to as compound 1, which exerts dual anticancer mechanisms. Compound 1 demonstrated potent inhibition of PARP7 enzymatic activity in biochemical assays and markedly reduced global mono-ADP-ribosylation (MARylation) in PARP7-inducible SK-MES-1 cells, thereby confirming its activity at the cellular level. From an IO perspective, compound 1 robustly induced interferon-stimulated gene (ISG) expression in RAW-Lucia ISG cells and various cancer cell lines. It also enhanced the activation of multiple immune cell subsets, showing pronounced effects particularly under TME-mimicking conditions. Compound 1 exhibited strong monotherapy activity in syngeneic tumor models and achieved complete responses (CR) when combined with anti-PD-1 or standard chemotherapies. Beyond immune modulation, PARP7 inhibition also mediates tumor-intrinsic growth inhibition. We identified a chromatin-associated trapping mechanism as a primary driver of these intrinsic effects. Correspondingly, compound 1 produced potent growth inhibition across multiple cancer cell lines, including NCI-H1373, and significantly suppressed tumor growth in xenograft models. Notably, across both mechanisms, compound 1 demonstrated comparable or superior activity to RBN2397, a PARP7 inhibitor under clinical evaluation. In summary, our findings highlight PARP7 inhibition as a promising therapeutic strategy that integrates immune activation with tumor-intrinsic growth inhibition. The novel PARP7 inhibitor, compound 1, consistently demonstrated this dual mechanism across diverse preclinical models, supporting its potential as a next-generation therapeutic candidate with both immune-mediated and tumor-intrinsic antitumor activity. Citation Format: Dajeong Kim, Iksoo Jang, Daehyeon Seong, Jeongyoon Shin, Kyu Hwan Kim, SeungHyun Song, Joon Yonug Hwang, Hong Sik Han, Kyung Seok Lee, Boram Lee, Soo-Jung Choi, Song-Yi Lee, Dae Young Lee, Jinhoon Jeong, Hojeong Hong, Haneol Kim, Jongho Cho, Ki Moon Ryu, Mi-Kyung Kim. A novel PARP7 inhibitor exhibits dual antitumor activity through immune activation and tumor-intrinsic growth inhibition [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 4567.

The rising global prevalence of obesity and its associated health problems necessitate effective intervention strategies. Historically, many anti-obesity medications have been developed and later withdrawn because of unfavorable adverse event profiles. By contrast, recently introduced glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) demonstrate remarkable efficacy for weight loss. Furthermore, they confer beneficial effects on cardiovascular and renal outcomes and metabolic dysfunction-associated liver disease. Despite these benefits, adverse events such as retained gastric content and pulmonary aspiration remain a concern. Consequently, this review summarizes current evidence and offers clinical guidance on GLP-1 RA-related adverse effects.

Background/Objective:Gastric cancer (GC) is a major cause of cancer mortality worldwide. We evaluated whether oral microbiota could be sensitive, specific, and non-invasive markers for early GC detection. Materials and methods:Saliva samples were analyzed using 16S rRNA sequencing, and oral microbial markers were validated using an internal validation dataset. Machine learning was used to identify key genera, and functional associations were inferred using Kyoto Encyclopedia of Genes and Genomes pathway and ortholog analyses. Blood samples were also collected, and plasma cytokines were quantified by enzyme-linked immunosorbent assay (ELISA) for pathway-level interpretations. Results:Eight genera-Lautropia, Megasphaera, Ralstonia, Pseudomonas, Peptostreptococcus, Anaerovorax, Fusobacterium, and Neisseria-were validated as diagnostic microbial markers (area under the receiver operating characteristic curve [AUC] = 0.91). Megasphaera and Ralstonia were enriched in GC, whereas Lautropia was depleted and associated with reduced risk. These genera may be functionally linked to pathways involved in GC progression, including NF-κB, IL-6, STAT3, TGF-β1, and Smad2/3. The proposed classification method effectively identified early-stage and tumor-marker-negative GCs, underscoring its clinical translation potential. Conclusions:Oral microbial markers, including Ralstonia, Megasphaera, and Lautropia, may serve as non-invasive diagnostic markers for GC and may be related to carcinogenic signaling activity.

Abstract Recently, ferroptosis has emerged as a pathogenic mechanism that drives metabolic dysfunction-associated steatohepatitis (MASH); however, the upstream triggers and their relevance to fibrosis remain poorly understood. Here we identified dietary cholesterol-induced ferroptosis and the downregulation of peroxisome proliferator-activated receptor delta (PPARδ) as central drivers of MASH pathogenesis. To investigate this, human liver samples and cholesterol-enriched dietary murine models of MASH were examined in parallel with mechanistic studies in hepatocytes and hepatic stellate cells (HSCs). Cholesterol-induced MASH was associated with pronounced hepatic lipid peroxidation and the selective downregulation of PPARδ. The loss of PPARδ disrupted redox homeostasis and sensitized hepatocytes to ferroptosis, whereas exosomal double-stranded DNA released from ferroptotic hepatocytes activated STING–TBK1–IRF3 and induced expression of profibrotic genes in HSCs. These effects were reversed by either overexpression of hepatocyte-specific PPARδ or pharmacologic treatment with DN203316, a novel and highly selective PPARδ agonist. In vivo, DN203316 mitigated ferroptosis, inflammation and fibrosis without inducing metabolic derangement. These findings were substantiated by clinical data demonstrating a marked increase in lipid peroxidation and STING-driven HSC activation in liver tissues from patients with MASH. In conclusion, PPARδ is a key regulator of cholesterol-induced ferroptosis and exosome-mediated fibrogenic signaling in MASH. DN203316 offers a promising therapeutic strategy to suppress ferroptosis, disrupt hepatocyte–HSC crosstalk and attenuate disease progression.

Growing evidence suggests that lipid metabolic reprogramming occurs in oral cancer (OC). We characterized circulating metabolic alterations associated with lipid metabolic reprogramming in OC. Semi-targeted and targeted plasma metabolomic profiling was performed in a discovery cohort (182 OC, 364 healthy controls [HC]) followed by independent external validation (52 OC, 52 HC). Machine learning approaches were used to identify plasma metabolites with strong discriminatory performance between patients with OC and healthy controls. Targeted validation confirmed consistent metabolic changes. Namely, three medium-chain acylcarnitines-decanoyl-, octanoyl-, and hexanoylcarnitine-were markedly downregulated in OC plasma, demonstrating consistent and reproducible discrimination during external validation (AUC = 0.941, 95% CI: 0.877-0.988). Pathway enrichment analysis further suggested altered β-oxidation and glycerophospholipid metabolism in OC. We also observed elevated carnitine palmitoyltransferase 1 (CPT1) expression in OC tissues and cells. Moreover, pharmacological inhibition of CPT1 suppressed OC cell growth and altered acylcarnitine profiles. These findings support an association between circulating acylcarnitine alterations and CPT1-related lipid metabolic reprogramming in OC. Furthermore, they provide biological context supporting the association between circulating metabolic alterations and CPT1-related lipid metabolic reprogramming in OC.

Patient-derived organoids (PDOs) can recapitulate selected features of original tumors and provide a useful system for studying epithelial ovarian cancer (EOC) in three-dimensional culture. Nonetheless, the protocol to generate EOC-PDOs has not yet been standardized. We therefore empirically refined the culture conditions and medium composition, considering the protocol effective when EOC PDOs were successfully established in five consecutive attempts. Tissue and ascites samples (from 29 and 8 patients, respectively) were used and the Syringe-extruded Organoid Basement membrane extract Assembly (SOBA) fragment culture method applied. Selected similarities in cell morphology, marker expression, and detectable alterations between organoids and patient-matched tumor tissue were assessed using pairwise comparisons. The refined workflow used a culture medium containing recombinant human R-Spondin 1 protein (250 ng/mL), Noggin, and NRG1, factors implicated in organoid maintenance and expansion. Ultimately, 31 EOC organoid lines successfully generated from 82.8% (24/29) of tissue and 87.5% (7/8) of ascites samples. The SOBA technique increased the 10 day PDO yield by 2.75-fold relative to the surface-attached dome method (p < 0.0001). This empirically refined workflow can be adjusted for specific experimental applications; however, further validation across larger and clinically diverse EOC cohorts is required.

Acute arterial hypoxemia frequently occurs in perioperative and critical care settings; however, the dynamic changes in endogenous biomarkers under these conditions remain poorly characterized. This study aimed to identify which among carboxyhemoglobin (COHb), methemoglobin (MetHb), and lactate best tracks the severity of acute arterial desaturation, and to explore potential ethnic differences in their responses. Data were retrospectively analyzed from four controlled desaturation studies involving 48 healthy volunteers (32 Korean and 16 African). Participants inhaled a hypoxic gas mixture of air and nitrogen to maintain arterial oxygen saturation (SaO₂) between 70% and 100%. Arterial blood samples were collected at each target SaO₂ level to measure COHb, MetHb, and lactate concentrations using CO-oximetry. Linear mixed-effects models (LMMs) were used to quantify the association between SaO₂ and each biomarker while accounting for repeated measurements. A total of 1,194 arterial samples from 48 participants were analyzed. Across SaO₂ ranges of 70-80%, 80-90%, and 90-100%, COHb exhibited the largest relative change among the three biomarkers (P < 0.001). LMM analysis showed a significant association between decreasing SaO₂ and increasing COHb (β₁=-0.0123, P < 0.001). In contrast, no significant associations were observed for MetHb (β₁=0.0003, P = 0.677) or lactate (β₁=-0.0011, P = 0.175). In subgroup analyses, Korean participants demonstrated significantly greater COHb elevations than African participants with increasing severity of arterial desaturation (P < 0.001). Among the evaluated endogenous biomarkers, COHb most closely tracked the severity of acute arterial desaturation. The greater COHb response observed in Korean participants is hypothesis-generating and suggests possible ethnic variability in physiological responses to controlled arterial desaturation.Clinical trial registration: Clinical Research Information Service (CRIS), Republic of Korea (http://cris.nih.go.kr) KCT0008376, KCT0008746, KCT0009938, and KCT0010039.

Lipopolysaccharide (LPS) exacerbates liver injury by activating various inflammatory pathways. Clusterin, a glycoprotein involved in lipid transport, and cytoprotection, is known to have inhibitory effects on liver steatosis and fibrosis. In this study, we investigated the role of clusterin in regulating LPS-induced liver injury and its effects on liver injury in C57BL/6 mice and clusterin knockout mice injected with LPS for 3 h. Primary Kupffer cells (KCs) and hepatocytes (HCs) were isolated from these mice and examined using immunohistochemistry, real-time RT-PCR, ELISA, and western blot analysis to assess the effects of clusterin. Clusterin deficiency significantly exacerbated LPS-induced liver injury, as evidenced by increased inflammatory cell infiltration, elevated serum alanine aminotransferase and aspartate aminotransferase levels, and upregulated expression of pro-inflammatory cytokines and components of the NLRP3 inflammasome. By contrast, overexpression of clusterin in primary Kupffer cells and hepatocytes significantly reduced these inflammatory markers. Furthermore, the protective mechanism of clusterin involved inhibition of the STAT3 signaling pathway. These findings suggest that clusterin is a useful therapeutic target to modulate cytokine production and key inflammatory signaling pathways in inflammatory liver diseases.

Metabolic/bariatric surgery is an effective treatment for obesity and type 2 diabetes mellitus (T2DM), with sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) being the most common procedures. However, comparative data on their metabolic benefits in East Asian populations are limited. This multicenter retrospective cohort study assessed outcomes of SG and RYGB in Korean adults (BMI ≥ 30 kg/m²) with T2DM who underwent surgery between January 2019 and June 2021. The primary outcome was complete T2DM remission at 1 and 2 years postoperatively. Follow-up data were available for 271 patients at 1 year and 169 at 2 years. Unadjusted analysis showed lower complete remission rates in the RYGB group than the SG group at both 1 year (51.4