Anosmia, characterized by the loss of smell, is associated not only with dysfunction in the peripheral olfactory system but also with changes in several brain regions involved in olfactory processing. Specifically, the orbitofrontal cortex is recognized for its pivotal role in integrating olfactory information, engaging in bidirectional communication with the primary olfactory regions, including the olfactory cortex, amygdala, and entorhinal cortex. However, little is known about alterations in structural connections among these brain regions in patients with anosmia. In this study, highresolution T1-weighted images were obtained from participants. Utilizing the volumes of key brain regions implicated in olfactory function, we employed a structural covariance approach to investigate brain reorganization patterns in patients with anosmia (n=22) compared to healthy individuals (n=30). Our structural covariance analysis demonstrated diminished connectivity between the amygdala and entorhinal cortex, components of the primary olfactory network, in patients with anosmia compared to healthy individuals (z=-2.22, FDR-corrected p=0.039). Conversely, connectivity between the orbitofrontal cortex—a major region in the extended olfactory network—and amygdala was found to be enhanced in the anosmia group compared to healthy individuals (z=2.32, FDR-corrected p=0.039). However, the structural connections between the orbitofrontal cortex and entorhinal cortex did not differ significantly between the groups (z=0.04, FDR-corrected p=0.968). These findings suggest a potential structural reorganization, particularly of higher-order cortical regions, possibly as a compensatory effort to interpret the limited olfactory information available in individuals with olfactory loss.

Objective: This study aimed to determine the clinical advantage of spindle-view intracytoplasmic sperm injection (SVICSI; a novel technology) over conventional intracytoplasmic sperm injection (cICSI) in patients with poor ovarian response (POR) and previous implantation failure. Methods: The study included 37 patients who underwent SVICSI followed by fresh embryo transfer (FET) at a single fertility clinic from January to December 2022, 58 patients who underwent cICSI followed by FET at the same fertility clinic from January to December 2021 as a control group. All study participants met the Bologna criteria for POR and had at least three or more previous failed embryo transfers. Results: The number of blastocyst transfers was significantly higher in the SVICSI group than in the cICSI group. A good-quality cleavage embryo rate, blastocyst rate, and good-quality blastocyst rate were also significantly higher in the SVICSI group than in the cICSI group. There were no significant differences in the rates of fertilization, implantation, clinical pregnancy, or clinical abortion between the two groups. Conclusion In patients with POR, those who underwent SVICSI appeared to have better embryos than those who underwent cICSI. However, whether SVICSI improved clinical outcomes such as implantation and pregnancy rates cannot be proven.

Purpose: To assess the added value of radiomics models from preoperative chest CT in predicting the presence of spread through air spaces (STAS) in the early stage of surgically resected lung adenocarcinomas using multiple validation datasets. Materials and Methods: This retrospective study included 550 early-stage surgically resected lung adenocarcinomas in 521 patients, classified into training, test, internal validation, and temporal validation sets (n=211, 90, 91, and 158, respectively). Radiomics features were extracted from the segmented tumors on preoperative chest CT, and a radiomics score (Rad-score) was calculated to predict the presence of STAS. Diagnostic performance of the conventional model and the combined model, based on a combination of conventional and radiomics features, for the diagnosis of the presence of STAS were compared using the area under the curve (AUC) of the receiver operating characteristic curve. Results: Rad-score was significantly higher in the STAS-positive group compared to the STAS-negative group in the training, test, internal, and temporal validation sets. The performance of the combined model was significantly higher than that of the conventional model in the training set {AUC: 0.784 [95% confidence interval (CI): 0.722–0.846] vs. AUC: 0.815 (95% CI: 0.759–0.872), p=0.042}. In the temporal validation set, the combined model showed a significantly higher AUC than that of the conventional model (p=0.001). The combined model showed a higher AUC than the conventional model in the test and internal validation sets, albeit with no statistical significance. Conclusion A quantitative CT radiomics model can assist in the non-invasive prediction of the presence of STAS in the early stage of lung adenocarcinomas.

Objective: To validate a simplified ordinal scoring method, referred to as modified length-based grading, for assessing coronary artery calcium (CAC) severity on non-electrocardiogram (ECG)-gated chest computed tomography (CT). Materials and Methods: This retrospective study enrolled 120 patients (mean age ± standard deviation [SD], 63.1 ± 14.5 years; male, 64) who underwent both non-ECG-gated chest CT and ECG-gated cardiac CT between January 2011 and December 2021. Six radiologists independently assessed CAC severity on chest CT using two scoring methods (visual assessment and modified length-based grading) and categorized the results as none, mild, moderate, or severe. The CAC category on cardiac CT assessed using the Agatston score was used as the reference standard. Agreement among the six observers for CAC category classification was assessed using Fleiss kappa statistics. Agreement between CAC categories on chest CT obtained using either method and the Agatston score categories on cardiac CT was assessed using Cohen’s kappa. The time taken to evaluate CAC grading was compared between the observers and two grading methods. Results: For differentiation of the four CAC categories, interobserver agreement was moderate for visual assessment (Fleiss kappa, 0.553 [95% confidence interval {CI}: 0.496–0.610]) and good for modified length-based grading (Fleiss kappa, 0.695 [95% CI: 0.636–0.754]). The modified length-based grading demonstrated better agreement with the reference standard categorization with cardiac CT than visual assessment (Cohen’s kappa, 0.565 [95% CI: 0.511–0.619 for visual assessment vs. 0.695 [95% CI: 0.638–0.752] for modified length-based grading). The overall time for evaluating CAC grading was slightly shorter in visual assessment (mean ± SD, 41.8 ± 38.9 s) than in modified length-based grading (43.5 ± 33.2 s) (P < 0.001). Conclusion The modified length-based grading worked well for evaluating CAC on non-ECG-gated chest CT with better interobserver agreement and agreement with cardiac CT than visual assessment.

Complex regional pain syndrome (CRPS) is a chronic neuropathic pain disorder. Pain catastrophizing, characterized by magnification, rumination, and helplessness, increases perceived pain intensity and mental distress in CRPS patients. As functional connectivity patterns in CRPS remain largely unknown, we aimed to investigate functional connectivity alterations in CRPS patients and their association with pain catastrophizing using a whole-brain analysis approach. Twenty-one patients with CRPS and 49 healthy controls were included in the study for clinical assessment and resting-state functional magnetic resonance imaging. Between-group differences in whole-brain functional connectivity were examined through a Network-based Statistics analysis. Associations between altered functional connectivity and the extent of pain catastrophizing were also assessed in CRPS patients. Relative to healthy controls, CRPS patients showed higher levels of functional connectivity in the bilateral somatosensory subnetworks (components 1~2), but lower functional connectivity within the prefronto-posterior cingulate (component 3), prefrontal (component 4), prefronto-parietal (component 5), and thalamo-anterior cingulate (component 6) subnetworks (p<0.05, family-wise error corrected). Higher levels of functional connectivity in components 1~2 (β=0.45, p=0.04) and lower levels of functional connectivity in components 3~6 (β=-0.49, p=0.047) were significantly correlated with higher levels of pain catastrophizing in CRPS patients. Higher functional connectivity in the somatosensory subnetworks implicating exaggerated pain perception and lower functional connectivity in the prefronto-parieto-cingulo-thalamic subnetworks indicating impaired cognitive-affective pain processing may underlie pain catastrophizing in CRPS.

Objective: T1 mapping provides valuable information regarding cardiomyopathies. Manual drawing is time consuming and prone to subjective errors. Therefore, this study aimed to test a DL algorithm for the automated measurement of native T1 and extracellular volume (ECV) fractions in cardiac magnetic resonance (CMR) imaging with a temporally separated dataset. Materials and Methods: CMR images obtained for 95 participants (mean age ± standard deviation, 54.5 ± 15.2 years), including 36 left ventricular hypertrophy (12 hypertrophic cardiomyopathy, 12 Fabry disease, and 12 amyloidosis), 32 dilated cardiomyopathy, and 27 healthy volunteers, were included. A commercial deep learning (DL) algorithm based on 2D U-net (Myomics-T1 software, version 1.0.0) was used for the automated analysis of T1 maps. Four radiologists, as study readers, performed manual analysis. The reference standard was the consensus result of the manual analysis by two additional expert readers. The segmentation performance of the DL algorithm and the correlation and agreement between the automated measurement and the reference standard were assessed. Interobserver agreement among the four radiologists was analyzed. Results: DL successfully segmented the myocardium in 99.3% of slices in the native T1 map and 89.8% of slices in the post-T1 map with Dice similarity coefficients of 0.86 ± 0.05 and 0.74 ± 0.17, respectively. Native T1 and ECV showed strong correlation and agreement between DL and the reference: for T1, r = 0.967 (95% confidence interval [CI], 0.951–0.978) and bias of 9.5 msec (95% limits of agreement [LOA], -23.6–42.6 msec); for ECV, r = 0.987 (95% CI, 0.980–0.991) and bias of 0.7% (95% LOA, -2.8%–4.2%) on per-subject basis. Agreements between DL and each of the four radiologists were excellent (intraclass correlation coefficient [ICC] of 0.98–0.99 for both native T1 and ECV), comparable to the pairwise agreement between the radiologists (ICC of 0.97–1.00 and 0.99–1.00 for native T1 and ECV, respectively). Conclusion The DL algorithm allowed automated T1 and ECV measurements comparable to those of radiologists.

Objective: We aimed to evaluate the ostium of right coronary artery of anomalous origin from the left coronary sinus (AORL) with an interarterial course throughout the cardiac cycle on CT and analyze the clinical significance of the ostial findings. Materials and Methods: From January 2011 to December 2015, 68 patients (41 male, 57.3 ± 12.1 years) with AORL with an interarterial course and retrospective cardiac CT data were included. AORL was classified as high or low ostial location based on the pulmonary annulus in the diastolic and systolic phases on cardiac CT. In addition, the height, width, height/width ratio, area, and angle of the ostium were measured in both cardiac phases. After cardiac CT, patients were followed until December 31, 2020 for major adverse cardiac events (MACE). Clinical and CT characteristics associated with MACE were explored using Cox regression analysis. Results: During a median follow-up period of 2071 days (interquartile range, 1180.5–2747.3 days), 13 patients experienced MACE (19.1%, 13/68). Seven (10.3%, 7/68) had the ostial location change from high in the diastolic phase to low in the systolic phase. In the univariable analysis, younger age (hazard ratio [HR] = 0.918, p < 0.001), high ostial location (HR = 4.008, p = 0.036), larger height/width ratio (HR = 5.621, p = 0.049), and smaller ostial angle (HR = 0.846, p = 0.048) in the systolic phase were significant predictors of MACE. In multivariable cox regression analysis, younger age (adjusted HR = 0.917, p = 0.002) and high ostial location in the systolic phase (adjusted HR = 4.345, p = 0.026) were independent predictors of MACE. Conclusion The ostial location of AORL with an interarterial course can change during the cardiac cycle, and high ostial location in the systolic phase was an independent predictor of MACE.

BACKGROUND/OBJECTIVES: Ginseng extract (GSE) and taurine (TR) are widely used antifatigue resources in functional foods. However, the mechanism underlying the antifatigue effects of GSE and TR are still unclear. Hence, we investigated whether GSE and TR have synergistic effects against fatigue in mice.MATERIALS/METHODS: L6 cells were treated with different concentrations of TR and GSE, and cell viability was determined using 2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium. Oxidative stress was analyzed by immunocytochemistry using MitoTracker™ Red FM and an anti-8-oxoguanine antibody. Respiratory gas analysis was performed to investigate metabolism. Expression of an activated protein kinase was analyzed using immunohistochemistry. Gene expression of cluster of differentiation 36 and pyruvate dehydrogenase lipoamide kinase isozyme 4 was measured using reverse transcription– polymerase chain reaction. Mice were orally administered TR, GSE, or their combination for 30 days, and then fatigue-related parameters, including lactate, blood urea nitrogen, and glycogen, were measured after forced swimming. RESULTS: TR and GSE reduced oxidative stress levels in hydrogen peroxide-stimulated L6 cells and enhanced the oxygen uptake and lipid metabolism in mice after acute exercise. After oral administration of TR or GSE for 30 days, the fatigue-related parameters did not change in mice. However, the mice administered GSE (400 mg/kg/day) alone for 30 days could swim longer than those from the other groups. Further, no synergistic effect was observed after the swimming exercise in mice treated with the TR and GSE combination for 30 days. CONCLUSIONS Taken together, our data suggest that TR and GSE may exert antifatigue effects in mice after acute exercise by enhancing oxygen uptake and lipid oxidation.

Abstinence from prolonged psychostimulant use prompts stimulant withdrawal syndrome. Molecular adaptations within the dorsal striatum have been considered the main hallmark of stimulant abstinence. Here we explored striatal miRNA-target interaction and its impact on circulating miRNA marker as well as behavioral dysfunctions in methamphetamine (MA) abstinence. We conducted miRNA sequencing and profiling in the nonhuman primate model of MA abstinence, followed by miRNA qPCR, LC-MS/MS proteomics, immunoassays, and behavior tests in mice. In nonhuman primates, MA abstinence triggered a lasting upregulation of miR-137 in the dorsal striatum but a simultaneous downregulation of circulating miR-137. In mice, aberrant increase in striatal miR-137-dependent inhibition of SYNCRIP essentially mediated the MA abstinence-induced reduction of circulating miR-137. Pathway modeling through experimental deduction illustrated that the MA abstinence-mediated downregulation of circulating miR-137 was caused by reduction of SYNCRIP-dependent miRNA sorting into the exosomes in the dorsal striatum. Furthermore, diminished SYNCRIP in the dorsal striatum was necessary for MA abstinence-induced behavioral bias towards egocentric spatial learning. Taken together, our data revealed circulating miR-137 as a potential blood-based marker that could reflect MA abstinence-dependent changes in striatal miR-137/SYNCRIP axis, and striatal SYNCRIP as a potential therapeutic target for striatum-associated cognitive dysfunction by MA withdrawal syndrome.