Cancer immunotherapy represents a paradigm-shifting achievement in oncology. Particularly, chimeric antigen receptor (CAR)-T cell therapy utilizing genetically engineered T cells has produced remarkable clinical responses in hematological malignancies.However, significant challenges still remain including limited efficacy in solid tumors and critical safety concerns. The functionality of CAR-T cells depends on their synthetic receptor, CAR, which redirects T cell specificity and enhances effector functions.Therefore, optimal CAR engineering is crucial for successful development of CAR-T cell therapy. In this review, we discuss the limitations of current CAR screening methods, which primarily assess antigen binding affinity in vitro and often fail to predict T cell function and in vivo therapeutic performance. Advanced cell-based screening platforms have been developed to overcome these limitations. We overview the principles of these CAR screening systems utilizing reporter cell lines. While most are based on the detection of antigen binding properties or CAR-T cell activation markers, we emphasize a FRET-based immunological synapse biosensor as a powerful system that directly assesses CAR activation upon antigen binding. This platform offers significant advantages in speed and scalability for predicting CAR-T cell functionality. We also discuss recent advances in CAR library screening directly in primary T cells, which provides more physiologically relevant data. Such advanced platforms are essential to accelerate the development of safe and effective CAR-T therapy for solid tumors, ultimately expanding the therapeutic potential of this transformative cancer treatment.

Purpose: Previous studies from mostly Western populations have suggested possible associations between obesity and melanoma risk. This study aimed to investigate associations between obesity status and melanoma using a nationwide cohort of Koreans. Materials and Methods: A total of 4,441,403 adults who received a national health examination in 2012 were included from the Korean National Health Insurance Service database, and followed until December 31, 2022. Obesity status was defined based on the body mass index at the baseline health examination. Cox proportional hazards analyses were performed to evaluate associations between obesity status and incident melanoma, with adjustment for confounders. Stratified analyses were performed by sex and menopausal status (in women). Results: Overall, melanoma risk increased according to obesity status (p for trend=0.024); adjusted hazard ratios (95% confidence intervals) for melanoma risk were 0.766 (0.438–1.340) in underweight; 1.292 (1.072–1.557) in overweight; 1.202 (1.002–1.442) in obesity; and 1.191 (0.798–1.778) in severe obesity compared to normal weight (reference). In stratified analyses, similar trends to those of the overall study population were observed among men and premenopausal women (p for trend=0.052 in men and 0.036 in premenopausal women). Among premenopausal women, the risk of melanoma increased linearly with obesity status. Meanwhile, among postmenopausal women, melanoma risk showed no significant difference or trend according to obesity status. Conclusion Overweight and obesity were associated with increased risk of melanoma in a population-based cohort of Koreans. Obese individuals, especially men and premenopausal women, may require more thorough prevention and screening strategies for melanoma.

OBJECTIVES: Kudoa septempunctata has been identified as the causative agent of food poisoning following the consumption of raw farmed Paralichthys olivaceus. However, cohort studies providing robust evidence for an association between K. septempunctata and gastrointestinal symptoms remain limited. This prospective cohort study investigated the association between the consumption of K. septempunctata–infected farmed P. olivaceus and the occurrence of gastrointestinal symptoms. METHODS: Individuals who purchased raw farmed P. olivaceus between 2020 and 2021 were selected as the study population. Study data included 2 rounds of questionnaire surveys administered before and after consumption, 2 muscle specimens obtained from each purchased fish, and human biological specimens collected from individuals who developed gastrointestinal symptoms within 24 hours after consumption. Data were analyzed using the chi-square test and t-test, and the association between consumption of K. septempunctata–infected farmed P. olivaceus and gastrointestinal symptoms was evaluated using relative risk estimates between exposure groups. RESULTS: The relative risk of gastrointestinal symptoms associated with exposure to K. septempunctata–infected P. olivaceus ranged from 71.2 (95% confidence interval [CI], 27.0 to 178.6) to 124.5 (95% CI, 43.5 to 355.0) across the 2 case definitions. A strong and statistically significant association was observed between exposure to K. septempunctata–infected P. olivaceus and the development of acute gastrointestinal symptoms. CONCLUSIONS These findings indicate both an association and a causal relationship between consumption of K. septempunctata–infected farmed P. olivaceus and the onset of gastrointestinal symptoms.

Infiltration and activation of peripheral immune cells are critical in the progression of multiple sclerosis and its experimental animal model, experimental autoimmune encephalomyelitis (EAE). This study investigates the role of high mobility group box 1 (HMGB1) in oligodendrocyte precursor cells (OPCs) in modulating pathogenic T cells infiltrating the central nervous system through the blood-brain barrier (BBB) by using OPC-specific HMGB1 knockout (KO) mice. We found that HMGB1 released from OPCs promotes BBB disruption, subsequently allowing increased immune cell infiltration. The migration of CD4+ T cells isolated from EAE-induced mice was enhanced when co-cultured with OPCs compared to oligodendrocytes (OLs). OPC-specific HMGB1 KO mice exhibited lower BBB permeability and reduced immune cell infiltration into the CNS, leading to less damage to the myelin sheath and mitigated EAE progression. CD4+ T cell migration was also reduced when co-cultured with HMGB1 knock-out OPCs. Our findings reveal that HMGB1 secretion from OPCs is crucial for regulating immune cell infiltration and provides insights into the immunomodulatory function of OPCs in autoimmune diseases.
Animals ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; HMGB1 Protein/deficiency* ; Mice, Knockout ; Oligodendrocyte Precursor Cells/immunology* ; Mice, Inbred C57BL ; CD4-Positive T-Lymphocytes/immunology* ; Cell Movement ; Blood-Brain Barrier/immunology* ; Mice ; Myelin Sheath/pathology* ; Disease Models, Animal ; Coculture Techniques ; Oligodendroglia/metabolism* ; Female ; Cells, Cultured

Background: Cutaneous angiosarcoma, a rare malignant tumor, is associated with high mortality and poor prognosis. Objective: This study aimed to analyze the clinicopathologic features of cutaneous angiosarcoma and identify the prognostic factors influencing survival. Methods: Medical records of patients diagnosed with cutaneous angiosarcoma between January 1995 and March 2023 were retrospectively reviewed. Demographic data, clinicopathologic features, and treatment modalities were analyzed to evaluate the correlation with overall survival (OS) and progression-free survival (PFS). A total of 70 patients were included in the study. Results: Their mean age at diagnosis was 71 years (range, 41–91 years). Of them, 57 (81.4%) were males. Five-year OS and PFS rates were 29.0% and 10.7%, respectively. In univariate analysis, a mass in the frontal area of the scalp showed significant associations with poorer PFS (hazard ratio [HR], 1.95; 95% confidence interval [CI], 1.07–3.55; p=0.029) and poorer OS (HR, 2.42; 95% CI, 1.22–4.80; p=0.011). Mass size exceeding 3 cm had a notable impact on PFS (HR, 3.41; 95% CI, 1.32–8.82; p=0.011) and remained a significant independent adverse prognosticator in multivariate analysis (HR, 4.55; 95% CI, 1.22–16.99; p=0.024). Conclusion Cutaneous angiosarcoma is characterized by an unfavorable prognosis, with a larger mass size identified as an independent prognostic factor.

Sensitive skin (SS) is increasingly recognized as a complex syndrome characterized by discomfort and heightened sensitivity to otherwise harmless stimuli, such as environmental changes, physical contact, and cosmetic products. This condition poses challenges in both diagnosis and treatment due to its variable presentation and subjective nature. The pathophysiological features of SS include neurogenic inflammation and small fiber neuropathy, largely driven by the hyperactivation of sensory nerves. This hyperactivation is closely associated with transient receptor potential (TRP) channels, particularly TRPV1, which contribute to the exaggerated sensory responses seen in SS. Furthermore, psychological factors like stress and anxiety, along with environmental stressors such as pollution and ultraviolet exposure, play significant roles in exacerbating symptoms. The diverse and individualized responses to stimuli make it difficult to establish standardized diagnostic criteria for SS, necessitating a combination of subjective diagnostic tools (e.g., the Sensitive Scale-10) and objective assessments (e.g., transepidermal water loss and lactic acid sting test) to accurately identify and assess SS. This paper provides a comprehensive review of SS, covering its definition, prevalence, pathogenesis, diagnostic challenges, and management strategies, and highlights the importance of personalized care in effectively managing SS and improving patient quality of life.

Background: There is a growing demand for extending dosing intervals of dupilumab injections in patients with atopic dermatitis (AD) due to treatment burden and side effects. However, studies on successful dose reduction in real-world settings are lacking. Objective: To assess the efficacy of a patient-centered dupilumab tapering regimen and to propose guidelines for target patients, appropriate intervals, and timing for tapering. Methods: This single-center retrospective study included moderate to severe adult AD patients who underwent at least 16 weeks of dupilumab treatment. Interval prolongation was considered in controlled patients assessed by Eczema Area and Severity Index (EASI) score and serum inflammatory markers after at least 40 weeks of treatment with a standard regimen. Logistic regression model with generalized estimating equations was used to compare repetitive measurements over time between the two groups. Results: A total of 52 patients were included with 11 patients extending intervals to 3–4 weeks without flare-ups. The mean duration of dupilumab treatment before tapering was 53.27 weeks. The tapering group exhibited significantly lower body mass index. All patients of the tapering group showed EASI scores under 4 and immunoglobulin E (IgE) levels under 1,000 IU/mL at week 40. EASI scores and IgE levels remained consistently low after dose reduction, with a mean follow-up time of 14.36 months. Conclusion Patients with extended dosing intervals demonstrated sustained effectiveness. Dose tapering might be a valuable option for non-obese patients with positive clinical response characterized by an EASI score under 4 and IgE levels under 1,000 at week 40.

Purpose: Pulmonary hypertension (PH) associated with bronchopulmonary dysplasia presents a significant clinical challenge in premature infants, often complicated by concurrent patent ductus arteriosus (PDA). The absence of age-specific treatments complicates disease management and outcome optimization. This study aimed to evaluate the impact of PH and PDA on mortality in premature infants and assess treatment outcomes of various treatment modalities, including pharmacological and procedural interventions. Methods: This retrospective cohort study included 1,708 premature infants (born at <37 weeks of gestation) treated at Jeonbuk National University Children’s Hospital between January 2013 and August 2023. All infants included in the analysis underwent echocardiographic evaluation. Patients were grouped based on PH and PDA diagnoses, and clinical outcomes, such as mortality, were compared. Statistical analyses, including receiver operating characteristic curves and logistic regression, were conducted. Results: PH and PDA were diagnosed in 46 (2.7%) and 257 (15.0%) patients, respectively. Patients with PH had lower mean gestational ages and birth weights than those of patients with PDA. The mortality rates were 21.7% in patients with PH and 8.2% in those with moderate-to-large PDA. Multivariate analysis identified PH as a significant predictor of mortality. There were no significant differences in mortality between the PDA-treated and untreated groups. Although iloprost use was initially associated with increased mortality, this association was not statistically significant after adjusting for gestational age and birth weight Conclusion PH significantly impacts mortality in premature infants, highlighting the need for early diagnosis and tailored treatments. Continued research is pertinent for enhancing outcomes and the quality of care.

Background: s/Aims: Microwave ablation (MWA) is an emerging ablative therapy that surpasses previous methods by achieving higher temperatures and creating larger ablation zones within shorter periods. This study compared the therapeutic outcomes of MWA with those of liver resection in real-world clinical practice. Methods: A total of 178 patients with 259 nodules who underwent MWA or liver resection between January 2015 and July 2023 were enrolled. Local tumor progression (LTP)-free survival, overall progression (OP)-free survival, and overall survival (OS) were assessed based on the treatment modality for the index nodule. Results: Of the 178 patients, 134 with 214 nodules underwent MWA, and 44 with 45 nodules underwent liver resection. The median follow-up period was 2.0±1.5 years. The annual incidence of LTP was 3.7% for MWA and 1.4% for liver resection. Treatment modality did not significantly affect LTP-free survival (hazard ratio, 0.61; 95% confidence interval, 0.14-2.69; P=0.511). For nodules larger than 3 cm, LTP-free survival was not affected by the treatment modality. Similarly, OP-free survival and OS were not influenced by treatment modality. Conclusions MWA and liver resection demonstrated comparable treatment outcomes in terms of local tumor control, overall recurrence, and survival. MWA may be an alternative treatment option for select patients; however, further studies are necessary to generalize these findings.