Conventional aryl hydrocarbon receptor (AhR) antagonists, which play a critical role in modulating tumor immune evasion, have shown limited clinical translation due to poor solubility, restricted systemic exposure, and dose-limiting toxicities. To overcome these limitations, we developed SB5794, a phosphate prodrug of the potent AhR antagonist SB2617, designed to improve aqueous solubility and pharmacokinetic properties. SB5794 exhibited markedly enhanced solubility and achieved more than six-fold higher systemic exposure in mice compared with SB2617, while fully retaining its in vitro AhR antagonistic activity. In syngeneic tumor models, SB5794 significantly inhibited tumor growth, and its combination with anti–PD-1 therapy further enhanced antitumor efficacy. However, repeated-dose studies revealed dose-dependent histopathological changes in the gastrointestinal tract, liver, and immune organs. Collectively, these findings demonstrate that SB5794 possesses improved drug-like properties and strong immunomodulatory activity, supporting its potential as a next-generation AhR-targeted immunotherapeutic candidate.

The valsalva maneuver is a gold standard test for evaluating cardiovascular autonomic function. By inducing characteristic heart rate and blood pressure changes across four phases, it allows simultaneous assessment of sympathetic and parasympathetic responses. Quantitative indices such as the valsalva ratio, pressure recovery time, and baroreflex sensitivities provide precise evaluation of autonomic reflex pathways. Specific patterns like the square-wave phenomenon offer diagnostic clues to differentiate peripheral from central autonomic disorders. This review summarizes the physiological mechanisms underlying the valsalva maneuver, key derived metrics, and examples of its clinical applications in diagnosing autonomic dysfunction in neurological disorders, including pure autonomic failure, Parkinson’s disease, and amyotrophic lateral sclerosis. Owing to its simplicity, noninvasiveness, and diagnostic utility, the valsalva maneuver remains a fundamental tool in clinical and research settings for autonomic assessment.

Purpose: While the benefit of neoadjuvant chemotherapy (NAC) has been established in human epidermal growth factor receptor 2 (HER2)-positive and triple-negative breast cancers, its effectiveness in achieving pathological complete response (pCR) and optimal patient selection in estrogen receptor (ER)-positive, HER2-negative breast cancers remain less clearly defined. This study aimed to identify immunohistochemistry (IHC)-based predictors of pCR and to develop a scoring model for ER-strong positive/HER2-negative breast cancer. Methods: Data from a prospective cohort were retrospectively analyzed. We included 522 patients with ER-strong positive/HER2-negative tumors who received NAC and surgery between 2008 and 2021. IHC markers including progesterone receptor (PR), Ki-67, epidermal growth factor receptor (EGFR), cytokeratin 5/6 (CK5/6), and p53 were evaluated to identify predictors of pCR. Independent predictors of pCR from multivariate logistic regression were used to develop a weighted 4-point model. Model performance was assessed using receiver operating characteristic analysis. The prognostic impact of pCR was evaluated using KaplanMeier and Cox regression analyses. Results: Independent predictors of pCR included PR-negative status, positivity for basallike markers (EGFR or CK5/6), and Ki-67 ≥ 50%. The scoring model demonstrated good discrimination for pCR (area under the curve = 0.754). pCR rates increased stepwise, with scores of 4.9% (low), 10.7% (intermediate), and 36.2% (high). In the high-score group, pCR was significantly associated with improved disease-free survival (hazard ratio [HR], 0.09; p = 0.023) and distant metastasis-free survival (HR, 0.11; p = 0.035), whereas no significant survival differences according to pCR status were observed in the low and intermediate score groups. Conclusion This IHC-based model predicts pCR and helps identify subgroups in which pCR is associated with meaningful survival benefit following NAC in ER-positive/HER2-negative breast cancers. High-scoring patients may benefit from NAC, while patients with low- or intermediatescores may be better managed with surgery and endocrine therapy. This model may support personalized treatment decisions regarding NAC.

Purpose: Lobular carcinoma In Situ (LCIS) is a noninvasive lesion associated with an increased risk of invasive cancer. Since its removal from the tumor, node, metastasis classification in the 8th edition of the American Joint Committee on Cancer (AJCC) guidelines, the clinical management of LCIS has shifted from surgery to surveillance. However, studies focusing on the risk and associated factors for invasive cancer development in pure LCIS without ductal carcinoma In Situ (DCIS) or invasive cancer remain limited. Methods: We retrospectively analyzed 106 patients diagnosed with pure LCIS between 2008 and 2018. This study evaluated the effect of tamoxifen use and histologic type on the development of invasive cancer. Results: All 106 patients underwent surgery, and nine (8.5%) developed invasive cancer over a median follow-up of 67.5 months. The incidence of invasive cancer was lower in the tamoxifen group (6.3%, n = 4) than in the non-tamoxifen group (11.9%, n = 5), although this difference was not statistically significant (p = 0.266). Pleomorphic LCIS had a significantly higher incidence of invasive cancer (30.0%, n = 3) than classic LCIS (6.3%, n = 6) (p = 0.045).Multivariable Cox regression analysis showed no significant difference in the risk of invasive cancer according to tamoxifen use (hazard ratio [HR], 2.031; 95% confidence interval [CI], 0.544–7.579; p = 0.292). However, pleomorphic LCIS showed a trend toward an increased risk of invasive cancer compared to classic LCIS (HR, 3.856; 95% CI, 0.922–16.126; p = 0.064). Conclusion Postoperative tamoxifen did not significantly lower invasive cancer development in patients with pure LCIS. Pleomorphic LCIS may carry a higher risk than classic LCIS. These findings require tailored follow-up and treatment strategies based on the histologic subtype of LCIS.

Objective: As the coronavirus disease 2019 (COVID-19) pandemic has been prolonged, the pre-hospital screening test performed in hospitals has changed from polymerase chain reaction (PCR) to rapid antigen test (RAT). RAT has lower sensitivity than PCR, but a lower cost and shorter test time. In the hospital where this study was conducted, the preadmission COVID-19 test was changed from PCR to RAT on February 24, 2023. This study compared the efficacy of PCR and RAT as the pre-admission COVID-19 test. Methods: This was a retrospective observational study comparing two periods, 90 days from November 25, 2022 to February 23, 2023, and 90 days from February 28, 2023 to May 29, 2023. Patients hospitalized from the emergency medical center during these two periods were included. Binomial logistic regression was used to compare the emergency department length of stay (ED LOS) between the two groups (PCR vs. RAT). Logistic regression was used to compare the mortality. Results: Four thousand seven hundred and thirty-eight patients were admitted through the emergency room: 2,202 patients in the PCR group and 2,443 patients in the RAT group. No statistically significant differences in the characteristics and severity were observed between the two groups. The mean ED LOS of PCR 5.07 hours (interquartile range, 3.80-6.75) was longer than RAT 3.65 hours (interquartile range, 2.83-4.68) (P<0.001). Mortality was higher in PCR 8.9% than RAT 6.6% (P=0.005). Conclusion The study showed that ED LOS and mortality were reduced when using RAT rather than PCR as a preadmission COVID-19 test.

Nevus unius lateris (NUL) is a variant of an epidermal nevus that involves a widespread body surface, especially half of the body, and its onset usually occurs at birth or early life. An increased risk of basal cell carcinoma (BCC) in epidermal nevus has also been reported. However, the exact incidence remains unknown. A 67-year-old female patient visited our dermatology clinic with black nodules protruding over multiple verrucous brownish patches and plaques on the right side of the trunk. The patient had congenital NUL. Black nodules were observed to develop several months previously and gradually enlarged. The skin biopsy of one black nodule was consistent with BCC. Subsequently, Mohs micrographic surgery was performed for the BCC. To date, there have been few reports of BCC arising within the nevus unius lateri. Herein, we report a rare case of BCC considered to originate from a congenital NUL.

Erosive adenomatosis of the nipple (EAN) is a rare benign entity that involves abnormal proliferation of the lactiferous ducts of the nipple and often presents with visible erosive lesions, erythema, or discharge. A 34-year-old female patient visited our clinic with erythematous patches and bloody discharge from the right nipple.Ultrasonography revealed a hypervascular lesion. A punch biopsy was performed, and histopathological examination confirmed the diagnosis of EAN. A 22-year-old female patient presented with a 4-year history of itchy erythematous eczematous patches with telangiectasia, crust, and bloody discharge in the areolar region. The punch biopsy results were consistent with those of EAN. The patient underwent total excision surgery. Herein, we report cases of EAN, which were difficult to differentiate from Paget's disease or nipple eczema, highlighting the need for clinicians to pay close attention.

Background: Basal cell carcinoma (BCC) is the most common type of skin cancer. In patients with darker skin, most BCCs are pigmented. Studies suggest that increased pigmentation in BCC may be inversely associated with tumor aggressiveness. Objective: This study analyzed the dermoscopic features and histopathologic patterns of BCCs to evaluate the correlation between BCC pigmentation and tumor aggressiveness. Methods: A total of 76 BCC lesions were included in this retrospective study. The Mohs micrographic surgery (MMS) stage and tumor depth were measured as indices of tumor aggressiveness. The Fontana–Masson stain was performed for the identification of melanin, and immunohistochemical analysis was performed using Melan-A and HMB-45 to identify melanocytes. Results: In MMS stage 1, the dermoscopic pigmentation value was 34.48%±14.22% (mean±standard deviation). In MMS stages 2 and 3, dermoscopic pigmentations were 13.72%±7.54% and 15.50%±17.52%, respectively. In the logistic regression model, higher dermoscopic pigmentation (95% confidence interval [CI], 0.68~0.99), melanin (95% CI, 0.63~0.89), and melanocyte-stained areas (95% CI, 0.70~0.92) were associated with a lower possibility of BCC tumor infiltration over the middle and lower layers. Conclusion We found an inverse correlation between the pigmentation and aggressiveness of BCCs. Clinicians can predict the subclinical infiltration depth of BCC on the basis of the pigmentation observed on dermoscopy. Pigmentation can be considered a favorable prognostic factor for BCC.

Background: The traditional nasolabial V-Y advancement flap is widely used for midface reconstruction, particularly for the lower third of the nose and upper lip, as its color and texture are similar to these areas. However, it provides insufficient tissue to cover large defects and cannot restore the nasal convexity, nasal ala, and adjacent tissues. The purpose of this study is to investigate the modified nasolabial V-Y advancement flap with extension limbs the along alar crease for the reconstruction of complex midface defects. Methods: A retrospective analysis of 18 patients, who underwent reconstruction with the modified nasolabial V-Y advancement flap, was performed between September 2014 and December 2022. An extension limb was added along the alar crease, adjacent to the defect area, and was hinged down as a transposition flap at the end of the advancement flap. Results: The extension limb along the alar crease successfully covered large and complicated defects, including those of the ala, the alar rim, the alar base, the nostrils, and the upper lip, with minor complications. Conclusion The alar crease is a good donor site for the reconstruction of large and complex nasal and upper lip defects.