Background and Objectives: Metoclopramide is an antagonist of dopamine D2 receptor and is capable of alleviating chemotherapy-induced nausea and vomiting. However, its underlying mechanisms and function in improving the efficiency of chemotherapy are not fully understood. In this study, we investigated the sensitizing effect of metoclopramide on the platinum-based drugs-mediated apoptosis in human head and neck cancer cells.Subjects and Method Apoptosis was analyzed using a cell-based cytometer. The protein expression and messenger ribonucleic acid (mRNA) levels were assessed by Western blotting and real-time polymerase chain reaction, respectively. Results: Metoclopramide sensitized the platinum-based drug (cisplatin and oxaliplatin)-mediated apoptosis in AMC-HN4 cells, but not in normal cells. Mechanistically, we found that metoclopramide decreased Mcl-1 protein expression through post-translational regulation. Moreover, the overexpression of Mcl-1 prevented apoptosis by combined treatment of metoclopramide and platinum-based drugs. Conclusion Metoclopramide induced proteasome-mediated Mcl-1 downregulation, resulting in increased sensitivity to platinum-based drugs.

Objective: To test the performance of an artificial intelligence-based computer-aided diagnosis (AI-CAD) designed for fullfield digital mammography (FFDM) when applied to synthetic mammography (SM). Materials and Methods: We analyzed 501 women (mean age, 57 ± 11 years) who underwent preoperative mammography and breast cancer surgery. This cohort consisted of 1002 breasts, comprising 517 with cancer and 485 without. All patients underwent digital breast tomosynthesis (DBT) and FFDM during the preoperative workup. The SM is routinely reconstructed using DBT. Commercial AI-CAD (Lunit Insight MMG, version 1.1.7.2) was retrospectively applied to SM and FFDM to calculate the abnormality scores for each breast. The median abnormality scores were compared for the 517 breasts with cancer using the Wilcoxon signed-rank test. Calibration curves of abnormality scores were evaluated. The discrimination performance was analyzed using the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity using a 10% preset threshold. Sensitivity and specificity were further analyzed according to the mammographic and pathological characteristics.The results of SM and FFDM were compared. Results: AI-CAD demonstrated a significantly lower median abnormality score (71% vs. 96%, P < 0.001) and poorer calibration performance for SM than for FFDM. SM exhibited lower sensitivity (76.2% vs. 82.8%, P < 0.001), higher specificity (95.5% vs.91.8%, P < 0.001), and comparable AUC (0.86 vs. 0.87, P = 0.127) than FFDM. SM showed lower sensitivity than FFDM in asymptomatic breasts, dense breasts, ductal carcinoma in situ, T1, N0, and hormone receptor-positive/human epidermal growth factor receptor 2-negative cancers but showed higher specificity in non-cancerous dense breasts. Conclusion AI-CAD showed lower abnormality scores and reduced calibration performance for SM than for FFDM.Furthermore, the 10% preset threshold resulted in different discrimination performances for the SM. Given these limitations, off-label application of the current AI-CAD to SM should be avoided.

Objective: The purpose of this study is to identify the types of pain changes that affect older Koreans, as well as their effects on depressive symptom. Methods: We analyzed the Korean Longitudinal Study of Aging data collected from 2010 to 2018. A data of total of 1,359 participants, aged 65 or older were used to estimate the change in pain. A latent growth model and growth mixture modeling were performed to estimate the overall change in pain and to categorize the types of pain changes. Results: The pain changes of older adults were classified into two categories: low-stable and high increasing. The depressive symptom showed a stronger relationship among the high-increasing type of pain than the low-stable type. The high-increasing type had a higher percentage of females, lower income, relatively low educational attainment, and a higher percentage of rural residents than the low-stable type. Conclusion The significance of this study is that it reiterated the importance of early pain diagnosis and intervention by identifying the types of pain changes in older adults and analyzing their effects on depressive symptoms. Therefore, it is especially important to pay attention to interventions that are designed to help vulnerable groups with a high risk of pain obtain effective pain management.

PURPOSE: The purpose of this study was to compare the surface characteristics and healing patterns after implantation of implants treated with SLA and those treated with both SLA and femtosecond laser. MATERIALS AND METHODS: A total of 10 male New Zealand white rabbits were used to compare recovery levels between implants treated with SLA (SLA group) and those treated with both SLA and femtosecond laser (SF group). The implants’ surface characteristics were determined through topographic evaluation, element analysis, surface roughness, and wettability evaluation. In total, 4 implants were placed in each rabbit (2 in each tibia), with 20 implants per treatment group. Using the implant stability quotient (ISQ), marginal bone volume, and histological analysis (bone-to-implant contact (BIC), bone volume/tissue volume (BV/TV)), and post implantation outcomes were assessed. Outcome data were analyzed using independent t-tests, Mann-Whitney U tests, Wilcoxon signed-rank tests, and one-way ANOVA (α = 0.05). RESULTS: No significant differences were noted between SLA and SF groups in terms of ISQ, marginal bone volume, BIC, and BV/TV (P > .05). However, significant differences in ISQ were observed within each group over time (P < .05). Furthermore, significant differences were noted in the marginal bone volume of the SF group (P < .05) and the BV/TV of the SLA group between weeks 4 and 6 (P < .05). CONCLUSION Surface treatment via SLA and femtosecond laser is feasible compared with SLA treatment alone in terms of ISQ, marginal bone volume, BIC, and BV/TV. However, further clinical research is warranted.

PURPOSE: The purpose of this clinical study was to evaluate the extent of intraoral occlusal adjustment required for zirconia crowns designed with a dynamic jaw motion tracking method compared to a conventional approach. MATERIALS AND METHODS: Fifteen patients needing zirconia crown restorations in the anterior or posterior regions participated in this study. Following tooth preparation, dynamic jaw motion tracking records were gathered using a tracking device. These records were imported into computer-aided design software and aligned with scanned upper and lower jaw data to design each crown's occlusal surface. Two crowns were fabricated for each patient: one using motion tracking data and another without it. Crowns were scanned pre- and post-adjustment following standard protocols. The scanned data were analyzed with 3D inspection software to calculate occlusal adjustments in the segmented occlusal area as root mean square values, with a paired t-test used for statistical analysis (α = 0.05). RESULTS: Crowns designed with motion tracking data required significantly less intraoral occlusal adjustment than those designed conventionally (P = .028). CONCLUSION Dynamic jaw motion tracking in crown design reduces the extent of intraoral occlusal adjustment, potentially enhancing clinical efficiency.

As research on the unique effects of space environment, especially microgravity and cosmic radiation, on the cardiovascular system is being conducted, research on the development of cardiovascular therapeutics using the space environment is attracting attention. This review comprehensively analyzes the current status and prospects of cardiovascular therapeutics development research utilizing space environment.Microgravity environment has been shown to have a positive effect on the proliferation and differentiation of cardiac progenitor cells and induced pluripotent stem cell-derived cardio myocytes. Cardiac tissue culture and organoid technology have enabled more effective drug screening and disease modeling than on the ground, and changes in gene expression such as Aquaporin-4 have been found to play an important role in cardiac function. Cosmic radiation can cause myocardial remodeling, fibrosis, and vascular endothelial dysfunction, and the underlying mechanisms of these effects include increased oxidative stress, promotion of inflammatory responses, deoxyribo nucleic acid damage, and cell death. Currently, the development of drugs that can prevent or treat cardiovascular damage caused by the space environment is in the early stages, and future research is expected to focus on developing personalized treatments and exploring the potential applications of space medicine research results to terrestrial medicine.

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.

Renal cell carcinoma (RCC) presents significant clinical challenges, highlighting the importance of understanding its molecular mechanisms. While store-operated Ca2+ entry (SOCE) is known to play an essential role in tumorigenesis and metastasis, its specific implications across various RCC subtypes remain underexplored.This study analyzed SOCE-related mRNA profiles from the KIRC and KIRP projects in The Cancer Genome Atlas (TCGA) database, focusing on differential gene expression and overall survival outcomes. Functional studies in clear cell RCC (Caki-1) and papillary RCC cell lines (pRCC, Caki-2) revealed increased expression of Orai1 and Orai3, along with STIM1, exhibited in both subtypes, with decreased STIM2 and increased Orai2 expression in pRCC. Notably, Orai3 expression had a gender-specific impact on survival, particularly in females with pRCC, where it inversely correlated with STIM2 expression. Functional assays showed Orai3 dominance in Caki-2 and Orai1 in Caki-1. Interestingly, 2-APB inhibited SOCE in Caki-1 but enhanced it in Caki-2, suggesting Orai3 as the primary SOCE channel in pRCC. Knockdown of Orai1 and Orai3 reduced cell migration and proliferation via regulating focal adhesion kinase (FAK) and Cyclin D1 in both cell lines. These findings highlight the critical roles of Orai1 and Orai3 in RCC metastasis, with Orai3 linked to poorer prognosis in females with pRCC. This study offers valuable insights into RCC diagnostics and potential therapeutic strategies targeting ORAI channels and STIM proteins.