Background: Though accumulating evidence suggests an association between childhood trauma and anhedonia, further analysis is needed to consider specific traumatic dimensions, both traits and state anhedonia, and the role of circulating proteins. Therefore, this study investigated the association between different types of childhood traumas and their influence on anhedonia-related symptoms, and to evaluate the influence of anhedonia traits and plasma proteins as mediators. Methods: This study included 170 patients with schizophrenia, bipolar disorder, major depressive disorder, and healthy controls aged 19–65 years. Multiple reaction monitoring was performed to quantify plasma proteins, and 464 proteins were analyzed. The association between childhood trauma dimensions, anhedonic traits, and related symptoms was analyzed with linear regression. A series of mediation analyses was performed to determine whether anhedonic traits and plasma proteins mediated the association between childhood trauma and anhedonia-related symptoms. Results: Childhood emotional neglect was significantly associated with anhedonic traits and anhedonia-related symptoms. Mediation analysis revealed that the indirect effect of anhedonic traits for childhood emotional neglect on anhedonia-related symptoms (effect = 0.037; bias-corrected CI, 0.009 to 0.070) was statistically significant. The indirect effect of plasma TNR5 for anhedonic traits on anhedonia-related symptoms was statistically significant (effect = −0.011; bias-corrected CI, −0.026 to −0.002). Serial mediation analysis revealed that the indirect effect of childhood emotional neglect on anhedonia-related symptoms via anhedonic traits and TNR5 was statistically significant (effect = 0.007; biascorrected CI, 0.001 to 0.017). Conclusion Anhedonic traits and plasma TNR5 protein levels serially mediated the association between childhood emotional neglect and anhedonia-related symptoms.The study highlights the importance of considering both psychopathological traits and biological correlates when investigating the association between childhood trauma and psychopathological symptoms.

Background: Although total intravenous anesthesia (TIVA) with propofol and remifentanil is frequently used to optimize intraoperative neurophysiological monitoring (IONM), the exact effect of remimazolam on IONM remains unknown. Here, we compared the effects of propofol and remimazolam along with remifentanil on IONM during TIVA. Methods: In this prospective, double-blind, randomized controlled trial, 64 patients requiring IONM during cervical spine surgery were administered either propofol (Group P) or remimazolam (Group R). The preoperative latencies of the somatosensory-evoked potentials (SEP; N20 for the median nerve and P37 for the tibial nerve) were measured. SEP latencies and amplitudes and motor-evoked potential (MEP) amplitudes were measured 30 min after anesthetic induction (T1), 30 min after surgical incision (T2), after laminectomy or discectomy (T3), immediately after plate insertion or pedicle screw fixation (T4), and before surgical wound closure (T5). The primary outcome was the between-group difference in the N20 latency changes measured at T1 and preoperatively. Results: The change in SEP latencies including N20 and P37 at T1 compared with preoperative time was not significantly different between Groups P and R. Except for the amplitude of the right abductor brevis, there was no significant group-by-time interaction effect for intraoperative MEP amplitudes or SEP latencies and amplitudes. Conclusions TIVA with remimazolam and remifentanil for cervical spine surgery yielded stable IONM, comparable to those observed with conventional TIVA with propofol and remifentanil. Further clinical trials are needed in other surgical contexts and with more diverse patient populations to determine the effects of remimazolam on IONM.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease that culminates in respiratory failure and death due to irreversible scarring of the distal lung. While initially considered a chronic inflammatory disorder, the aberrant function of the alveolar epithelium is now acknowledged as playing a central role in the pathophysiology of IPF. This study aimed to investigate the regenerative capacity of alveolar type 2 (AT2) cells using IPF-derived alveolar organoids and to examine the effects of disease progression on this capacity. Methods: Lung tissues from three pneumothorax patients and six IPF patients (early and advanced stages) were obtained through video-assisted thoracoscopic surgery and lung transplantation. HTII-280+ cells were isolated from CD31-CD45-epithelial cell adhesion molecule (EpCAM)+ cells in the distal lungs of IPF and pneumothorax patients using fluorescence-activated cell sorting (FACS) and resuspended in 48-well plates to establish IPF-derived alveolar organoids. Immunostaining was used to verify the presence of AT2 cells. Results: FACS sorting yielded approximately 1% of AT2 cells in early IPF tissue, and the number decreased as the disease progressed, in contrast to 2.7% in pneumothorax. Additionally, the cultured organoids in the IPF groups were smaller and less numerous compared to those from pneumothorax patients. The colony forming efficiency decreased as the disease advanced. Immunostaining results showed that the IPF organoids expressed less surfactant protein C (SFTPC) compared to the pneumothorax group and contained keratin 5+ (KRT5+) cells. Conclusion This study confirmed that the regenerative capacity of AT2 cells in IPF decreases as the disease progresses, with IPF-derived AT2 cells inherently exhibiting functional abnormalities and altered differentiation plasticity.

Background: Although total intravenous anesthesia (TIVA) with propofol and remifentanil is frequently used to optimize intraoperative neurophysiological monitoring (IONM), the exact effect of remimazolam on IONM remains unknown. Here, we compared the effects of propofol and remimazolam along with remifentanil on IONM during TIVA. Methods: In this prospective, double-blind, randomized controlled trial, 64 patients requiring IONM during cervical spine surgery were administered either propofol (Group P) or remimazolam (Group R). The preoperative latencies of the somatosensory-evoked potentials (SEP; N20 for the median nerve and P37 for the tibial nerve) were measured. SEP latencies and amplitudes and motor-evoked potential (MEP) amplitudes were measured 30 min after anesthetic induction (T1), 30 min after surgical incision (T2), after laminectomy or discectomy (T3), immediately after plate insertion or pedicle screw fixation (T4), and before surgical wound closure (T5). The primary outcome was the between-group difference in the N20 latency changes measured at T1 and preoperatively. Results: The change in SEP latencies including N20 and P37 at T1 compared with preoperative time was not significantly different between Groups P and R. Except for the amplitude of the right abductor brevis, there was no significant group-by-time interaction effect for intraoperative MEP amplitudes or SEP latencies and amplitudes. Conclusions TIVA with remimazolam and remifentanil for cervical spine surgery yielded stable IONM, comparable to those observed with conventional TIVA with propofol and remifentanil. Further clinical trials are needed in other surgical contexts and with more diverse patient populations to determine the effects of remimazolam on IONM.

Purpose: To investigate the clinical characteristics of South Korean patients with pericentral retinitis pigmentosa (RP) and to identify clinical biomarkers associated with rapid visual acuity decline based on baseline factors. Methods: This retrospective study included 59 eyes of 31 patients diagnosed with pericentral RP. Comprehensive ophthalmological examinations and genetic sequencing were conducted to assess the baseline characteristics. For biomarker analysis, eyes were categorized into two groups based on the annual rate of change in visual acuity. The clinical findings of the two groups were evaluated to identify the biomarkers associated with rapid loss of visual acuity. Results: Patients with pericentral RP in this study exhibited a mean best-corrected visual acuity of 0.17 ± 0.23 in logarithm of the minimum angle of resolution. The visual field test showed annular or semicircular scotoma with relatively preserved periphery and 27 eyes (45.8%) exhibited no macular complications in optical coherence tomography. Genetic analysis identified genes associated with previous typical and pericentral RP studies but also highlighted that many genetic causes of pericentral RP remain unidentified. Of the 55 eyes for which the rate of visual acuity change could be estimated, 18 exhibited an annual decline of ≥10%, whereas 37 showed an annual decline of <10%. Male sex and prolonged b-wave latency on dark-adapted 0.01 electroretinogram correlated with rapid visual acuity decline in the multivariate analysis. Conclusions South Korean patients with pericentral RP exhibited a milder phenotype compared to typical RP patients reported in previous studies. Genetic analysis revealed heterogeneity, with mutations in some genes commonly associated with milder forms of RP. Male sex and prolonged b-wave latency on dark-adapted 0.01 electroretinogram were significant biomarkers for predicting rapid visual acuity decline. Monitoring initial b-wave latency is important for predicting visual decline, particularly in male patients with pericentral RP.

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.

Background/Aims: As the number of lower gastrointestinal endoscopies and high-risk examinees increases, the incidence of adverse events associated with these endoscopies has also increased. Medical disputes and lawsuits related to adverse events are rapidly increasing. Methods: Medical disputes related to lower gastrointestinal endoscopy that had been filed in Korean Medical Dispute Mediation and Arbitration Agency (K-medi) from April 2012 to August 2020 were evaluated with the corresponding medical records and written appraisal. Facilities, patients, procedures, adverse events, and outcome-related variables related to medical disputes were analyzed. Results: As the number of lower gastrointestinal endoscopies in Korea increases each year, the number of medical disputes related to lower gastrointestinal endoscopy appraised by K-medi has also increased yearly during the same period. Among the 121 cases analyzed, 86 (71.1%) were conciliated and 35 (28.9%) were cosigned by prosecution. Perforations accounted for the largest proportion of cases (93 cases, 76.9%). Most patients (n = 119, 98.3%) underwent non-emergent procedures, and only 10 (8.3%) underwent them for therapeutic purposes. Approximately one-fifth of the patients (n = 25, 20.7%) died. Conclusions The number of medical disputes related to lower gastrointestinal endoscopy are increasing. To prevent this, it is important to review the data on existing cases and establish specific response guidelines.

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.